Tagged: Alzheimer’s disease Toggle Comment Threads | Keyboard Shortcuts

  • richardmitnick 8:08 am on January 8, 2018 Permalink | Reply
    Tags: Alzheimer’s disease, , ‘Trophic support’, , The ‘metabolic vulnerability’ hypothesis, Transneuronal spread, Two abnormal proteins: amyloid beta and tau,   

    From U Cambridge: “Advances in brain imaging settle debate over spread of key protein in Alzheimer’s” 

    U Cambridge bloc

    University of Cambridge

    05 Jan 2018
    Craig Brierley

    Recent advances in brain imaging have enabled scientists to show for the first time that a key protein which causes nerve cell death spreads throughout the brain in Alzheimer’s disease – and hence that blocking its spread may prevent the disease from taking hold.

    Alzheimer’s patients & carers. Credit: Global Panorama

    An estimated 44 million people worldwide are living with Alzheimer’s disease, a disease whose symptoms include memory problems, changes in behaviour and progressive loss of independence. These symptoms are caused by the build-up in the brain of two abnormal proteins: amyloid beta and tau. It is thought that amyloid beta occurs first, encouraging the appearance and spread of tau – and it is this latter protein that destroys the nerve cells, eating away at our memories and cognitive functions.

    Until a few years ago, it was only possible to look at the build-up of these proteins by examining the brains of Alzheimer’s patients who had died, post mortem. However, recent developments in positron emission tomography (PET) scanning have enabled scientists to begin imaging their build-up in patients who are still alive: a patient is injected with a radioactive ligand, a tracer molecule that binds to the target (tau) and can be detected using a PET scanner.

    In a study published today in the journal Brain, a team led by scientists at the University of Cambridge describe using a combination of imaging techniques to examine how patterns of tau relate to the wiring of the brain in 17 patients with Alzheimer’s disease, compared to controls.

    Quite how tau appears throughout the brain has been the subject of speculation among scientists. One hypothesis is that harmful tau starts in one place and then spreads to other regions, setting off a chain reaction. This idea – known as ‘transneuronal spread’ – is supported by studies in mice. When a mouse is injected with abnormal human tau, the protein spreads rapidly throughout the brain; however, this evidence is controversial as the amount of tau injected is much higher relative to brain size compared to levels of tau observed in human brains, and the protein spreads rapidly throughout a mouse’s brain whereas it spreads slowly throughout a human brain.

    There are also two other competing hypotheses. The ‘metabolic vulnerability’ hypothesis says that tau is made locally in nerve cells, but that some regions have higher metabolic demands and hence are more vulnerable to the protein. In these cases tau is a marker of distress in cells.

    The third hypothesis, ‘trophic support’, also suggests that some brain regions are more vulnerable than others, but that this is less to do with metabolic demand and more to do with a lack of nutrition to the region or with gene expression patterns.

    Thanks to the developments in PET scanning, it is now possible to compare these hypotheses.

    “Five years ago, this type of study would not have been possible, but thanks to recent advances in imaging, we can test which of these hypotheses best agrees with what we observe,” says Dr Thomas Cope from the Department of Clinical Neurosciences at the University of Cambridge, the study’s first author.

    Dr Cope and colleagues looked at the functional connections within the brains of the Alzheimer’s patients – in other words, how their brains were wired up – and compared this against levels of tau. Their findings supported the idea of transneuronal spread, that tau starts in one place and spreads, but were counter to predictions from the other two hypotheses.

    “If the idea of transneuronal spread is correct, then the areas of the brain that are most highly connected should have the largest build-up of tau and will pass it on to their connections. It’s the same as we might see in a flu epidemic, for example – the people with the largest networks are most likely to catch flu and then to pass it on to others. And this is exactly what we saw.”

    Professor James Rowe, senior author on the study, adds: “In Alzheimer’s disease, the most common brain region for tau to first appear is the entorhinal cortex area, which is next to the hippocampus, the ‘memory region’. This is why the earliest symptoms in Alzheimer’s tend to be memory problems. But our study suggests that tau then spreads across the brain, infecting and destroying nerve cells as it goes, causing the patient’s symptoms to get progressively worse.”

    Confirmation of the transneuronal spread hypothesis is important because it suggests that we might slow down or halt the progression of Alzheimer’s disease by developing drugs to stop tau from moving along neurons.

    Image: Artist’s illustration of the spread of tau filaments (red) throughout the brain. Credit: Thomas Cope.

    The same team also looked at 17 patients affected by another form of dementia, known as progressive supranuclear palsy (PSP), a rare condition that affects balance, vision and speech, but not memory. In PSP patients, tau tends to be found at the base of the brain rather than throughout. The researchers found that the pattern of tau build-up in these patients supported the second two hypotheses, metabolic vulnerability and trophic support, but not the idea that tau spreads across the brain.

    The researchers also took patients at different stages of disease and looked at how tau build-up affected the connections in their brains.

    In Alzheimer’s patients, they showed that as tau builds up and damages networks, the connections become more random, possibly explaining the confusion and muddled memories typical of such patients.

    In PSP, the ‘highways’ that carry most information in healthy individuals receives the most damage, meaning that information needs to travel around the brain along a more indirect route. This may explain why, when asked a question, PSP patients may be slow to respond but will eventually arrive at the correct answer.

    The study was funded by the NIHR Cambridge Biomedical Research Centre, the PSP Association, Wellcome, the Medical Research Council, the Patrick Berthoud Charitable Trust and the Association of British Neurologists.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    U Cambridge Campus

    The University of Cambridge (abbreviated as Cantab in post-nominal letters) is a collegiate public research university in Cambridge, England. Founded in 1209, Cambridge is the second-oldest university in the English-speaking world and the world’s fourth-oldest surviving university. It grew out of an association of scholars who left the University of Oxford after a dispute with townsfolk. The two ancient universities share many common features and are often jointly referred to as “Oxbridge”.

    Cambridge is formed from a variety of institutions which include 31 constituent colleges and over 100 academic departments organised into six schools. The university occupies buildings throughout the town, many of which are of historical importance. The colleges are self-governing institutions founded as integral parts of the university. In the year ended 31 July 2014, the university had a total income of £1.51 billion, of which £371 million was from research grants and contracts. The central university and colleges have a combined endowment of around £4.9 billion, the largest of any university outside the United States. Cambridge is a member of many associations and forms part of the “golden triangle” of leading English universities and Cambridge University Health Partners, an academic health science centre. The university is closely linked with the development of the high-tech business cluster known as “Silicon Fen”.

  • richardmitnick 11:36 am on December 25, 2017 Permalink | Reply
    Tags: Alzheimer’s disease, Amyloid plaques, , , Inflammasome, , The AD-afflicted brain is like a crime scene. The victims are masses of dead neurons that leave many parts of the brain shrunken.   

    From COSMOS: “Brain inflammation sows the seeds of Alzheimer’s” 

    Cosmos Magazine bloc

    COSMOS Magazine

    21 December 2017
    Elizabeth Finkel

    Amyloid plaques can be seen gumming up the spaces between neurons in this illustration. Juan Gaertner / Science Photo Library.

    When it comes to the perpetrator of Alzheimer’s disease (AD), the finger of blame has long pointed to hard deposits of protein in the brain known as amyloid plaques. But smouldering signs of inflammation are also clearly evident in the background.

    Now a paper in Nature reveals how the two processes connive. During inflammation, specks of a protein called ASC are released. Like the grit inside a pearl, they seed the deposition of amyloid. The authors – Carmen Venegas at the University of Bonn, Germany and colleagues – showed that in mice, removing the specks prevented the formation of amyloid and slowed progression of the disease.

    “The paper bridges different camps and puts inflammation front and centre as a potential cause of AD,” says Bryce Vissel, an AD researcher at the University of Technology, Sydney.

    The finding also suggests that anti-inflammatory drugs, particularly those that target the formation of the ASC specks, offer a new therapeutic way forward.

    “This is an extremely important paper for the Alzheimer’s field and is likely to greatly influence the way researchers think about potential Alzheimer’s treatment strategies going forward,” adds Vissel.

    The AD-afflicted brain is like a crime scene. The victims are masses of dead neurons that leave many parts of the brain shrunken. The suspects are many: alongside amyloid plaques, tangles of tau proteins inside the neurons have also been interrogated, and investigators find signs of riled-up immune cells called microglia everywhere they look.

    But amyloid plaques have been at the top of the list. That’s because people who inherit rare genetic forms of the disease also inherit abnormal genes that cause excessive production of sticky forms of amyloid protein that are more likely to aggregate into plaques. Assuming that the plaques were also the cause of neuron death in more common forms of AD, researchers have for the last three decades been developing plaque-busting drugs. But while some, like the promising antibody aducanumab, have scrubbed away plaque, so far they do not appear to have halted the disease.

    Given the dead end, many researchers have turned their interest to other suspects. An irritable brain has become a hot favourite. Those agitated microglia and the mobilizing chemicals factors they secrete are found all over the brains of AD sufferers. General signs of body inflammation in middle age also appear to correlate with an increased risk of AD in later life.

    The Venegas team decided to piece together the chain of events that occurs after microglia become irritated. A key occurrence is the formation of a protein complex inside them called an inflammasome. Like a smouldering fire, it continues to release inflammatory signals which mobilize other microglia.

    One of the other things the inflammasome does is to release tiny specks of aggregated ASC protein. The researchers had a hunch that ASC specks might be affecting the course of the disease. Not only are they visible in the brain tissue of people with AD, but mice studies had shown that when the formation of the inflammasome was impaired, the mice were protected from their version of the disease.

    To test if the specks played some role, the researchers carried out experiments in mice that are genetically engineered to overproduce amyloid plaque. Some of the mice were also engineered not to produce the ASC protein.

    For starters, the researchers found that mice lacking ASC produced less amyloid plaque and their disease appeared less severe: they performed better at memorizing mazes, for instance. When brain extracts from plaque-ridden mice were injected into young mice, they seeded the development of new amyloid plaques.

    But strikingly, if antibodies to ASC were injected at the same time, it interfered with the seeding.

    If the recipient animals lacked ASC altogether, no spreading was seen. ASC did indeed appear to be acting as the grit that seeded the plaque deposits.

    The findings show how inflammation and amyloid may collude in a vicious cycle to cause the disease. Amyloid deposits cause inflammation; inflammation releases ASC; ASC seeds the deposition of more amyloid plaque.

    What this means, explains senior author Michael Heneka, is that minor insults to the brain – perhaps a virus or mild injury – could snowball into a major inflammatory cascade that kills off neurons.

    So what’s to be done?

    Heneka points out that population studies already show the use of anti-inflammatory drugs like ibuprofen allay the onset of AD. But he says these drugs are too non-specific. Many drug companies are now focussed on finding drugs that inhibit the function of the inflammasome in a particular tissue. “This is all under way,” he says.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

  • richardmitnick 12:26 pm on August 28, 2017 Permalink | Reply
    Tags: Alzheimer’s disease, , , ,   

    From Brown: “Researchers seek to catch Alzheimer’s early by peeking into the eyes” 

    Brown University
    Brown University

    August 28, 2017
    David Orenstein

    Research spanning the academic-medical partnership among Brown University, Rhode Island Hospital and Butler Hospital is advancing the possibility that the retinas will give doctors a way to identify Alzheimer’s disease risk long before symptoms begin.

    Mark Wolff prepares for a series of retinal scans for a study that may help to determine whether the eyes provide a useful window into the early development of Alzheimer’s disease. Nicholas Dentamaro.

    Mark Wolff wanted to know. To him, the thought of suffering through Alzheimer’s disease the way his father did — without knowing, and without his family knowing, what he was up against until late in its progression— is worse than learning, even while he’s still perfectly healthy, that a possible precursor of the disease has gained a toehold.

    “I’m not a worrier by nature,” Wolff said. “I just don’t want to wind up like my dad. It was just a nightmare what happened to him. He didn’t get the medical attention he needed and his quality of life could have been better.”

    So Wolff, a lighting company executive from Bristol, R.I., enrolled in a trial at Butler Hospital and found out through a positron emission tomography (PET) scan of his brain that he has early signs of amyloid plaque. The presence of plaque, a tangle of proteins that could eventually cause the neurodegeneration of Alzheimer’s disease, is a risk factor — even so, Wolff might never develop the disease. Or if he does, it might not affect him for a decade or more.

    The trial, being conducted at both Butler and Rhode Island Hospital, is led by Dr. Stephen Salloway, a professor of neurology at Brown University and director of Butler’s Memory and Aging Program. It has two goals. One is to test whether the drug solanezumab will prevent or delay memory loss and slow amyloid plaque buildup in people at increased risk for Alzheimer’s. The other, via a sub-study launched at Butler Hospital, is to test whether a retinal scan can monitor that progress as well as the much more expensive PET scans. Salloway is working on the larger trial with Dr. Brian Ott, a Brown professor of neurology and director of the Alzheimer’s Disease and Memory Disorders Center at Rhode Island Hospital.

    As part of the research, Wolff returned to Butler on a warm summer afternoon for what unfolded like an eye doctor’s appointment. Nurse practitioner Brittany Dawson dilated Wolff’s eyes with drops. From there, he stared into the same optical coherence tomography (OCT) scanner that an ophthalmologist or optometrist would use to look for macular degeneration or glaucoma. For about 20 minutes, while postdoctoral researcher Dr. Jessica Alber operated the machine and guided him through the experiment, Wolff posed his retinas for multiple close-ups that will be independently inspected for the presence of amyloid plaques.

    Inspired in large part by research led by colleague Dr. Peter Snyder, a professor of neurology and ophthalmology at Brown and senior vice president and chief research officer at Lifespan, Salloway and Ott believe that the retina may provide a reliable reflection of early but significant Alzheimer’s disease risk in the brain. If so, that could vastly expand the number of people around the world who receive an early risk assessment and could save tremendous amounts of money compared to $5,000 PET scans, Snyder said.

    The best chance for treating Alzheimer’s, Snyder said, will be to identify and treat the disease long before symptoms arise, because by then too much damage may be done. Meanwhile, the need is so widespread that it must be done inexpensively and with non-invasive equipment as common as an OCT eye scanner. PET is both too costly and not widely available enough to be the first-line screening tool.

    “We have to identify markers that are accessible to point-of-care clinicians,” Snyder said. “The number of people with Alzheimer’s disease is going to triple over the next 50 years. We have to change the impact of this disease. If we don’t get this right, the burden on society is going to be devastating.”

    Snyder expects that doctors will need to combine several biomarkers to produce an estimate of patients’ eventual Alzheimer’s risk: family history, genetics, and cognitive and memory tests will likely combine with multiple retinal indicators into a comprehensive algorithm. Those with especially high emerging risk might then go on to PET scans and early-stage treatments — perhaps solanezumab — as those are proven, he said.

    The brain in the eyes

    The retina is a part of the central nervous system that doctors can see by opening nothing more than an eyelid.

    “Potentially, the eye could be the window to the brain in the fight against Alzheimer’s,” said Salloway, who along with Ott and Snyder is affiliated with the Brown Institute for Brain Science,

    The retina has the same biochemistry and similar organization and cell types, Snyder said, so it makes sense that it, too, would be similarly susceptible to amyloid plaques. It’s no surprise given that the retina forms out of the same tissue as the brain in just the first few weeks of an embryo’s development.

    Plaques pictured “Inclusion bodies” of amyloid plaque are visible in a subject’s retina in this scan published in Dr. Peter Snyder’s 2016 paper. Snyder et al.

    In recent years, scientists have noticed that amyloid plaques built up in the retinas. In 2016 in the journal Alzheimer’s and Dementia, Snyder and co-authors published a study of 63 cognitively normal adults with at least one parent with Alzheimer’s (just like Wolff) that compared the results of OCT scans with PET scans in the same patients. Snyder’s team found a significant relationship between amyloid levels in the cortex of the brain, as measured by PET, and the total surface area of what appear to be amyloid plaques visible in the retina.

    “Our findings support the hypothesis that retinal biomarkers could be a useful screening tool to distinguish individuals at risk for developing Alzheimer’s disease, and could be helpful in identifying ideal candidates for secondary prevention trials,” he and his co-authors wrote.

    That hypothesis is now being tested further in Salloway’s sub-study.

    In other recent work, Snyder’s research group led by Alber showed that retinal scans can also indicate other potential precursors of closely related neurodegenerative disorders, such as cerebral amyloid angiopathy.

    The group is also studying how OCT can image changes in the vasculature of the retina, because amyloid can attack and alter blood vessels as well as neurons. Finally, the researchers are measuring associations between the presence of amyloid plaque and the thickness of individual layers of the retina. In a recent presentation in London of a small study, the team reported that the retinal nerve fiber layer thins as amyloid plaque in the brain increases.

    Pushing the technology further

    As sensitive as conventional OCT has proven to be in measuring the retina, Snyder said, it could get even better through the work of Jonghwan Lee, an assistant professor of engineering at Brown.

    In his work to improve neural imaging, Lee has developed sophisticated algorithms that amplify the signal of OCT and reduce the noise. These improvements have allowed him to produce stunningly high-resolution imaging of blood flow — red blood cell by red blood cell — in even the tiniest capillaries of neural tissue. That means he might be able to very precisely observe some of the small but early changes in vasculature that Snyder is interested in.

    The two have begun to collaborate. Working in a mouse model of Alzheimer’s and with healthy controls, Lee hopes to track down the earliest vascular, neural and behavioral changes associated with the disease as the mice age.

    Brain veins. In stunning detail Brown engineer Jonghwan Lee can use retinal scanning technology to image the vasculature of neural tissue.
    Jonghwan Lee.

    “Our first hypothesis is that maybe alterations in vasculature and blood flow will appear in the brain first, so we are imaging the animal brain every month,” Lee said. “And at the same time we are testing the cognitive function of the animal and how it declines and we are looking at blood flow and vasculature in the retina.”

    “So we will make a bigger picture of which one is first, which one is earlier and how much it is earlier and significant,” Lee said.

    The goal would be to compile a predictive algorithm of the disease’s progression in the mouse from its very earliest stage using a similar combination of biomarkers — physiology, cognition and genetics — that Snyder suspects will need to be compiled for people.

    The study is very early stages, Lee said: “No one knows the exact answer yet.”

    ‘Better to know’

    In the exam room at Butler, Betty Wolff, Mark’s wife of 45 years, shared that it was initially hard for her to hear the results of the PET scan, but she agreed that it’s better to know. If the infusions he’ll begin later in the summer contain solanuzemab rather than the placebo and if the medication works, his enrollment in the trial might help to stop or slow the disease even before it even gets started. And at least if Wolff becomes symptomatic with Alzheimer’s down the road, the family will have had ample warning and will be able to manage the condition as well as possible, right from the start.

    None of those possibilities was available for Wolff’s dad, which is why he’s so eager to volunteer to advance this research. He’s no stranger to volunteering, having been a blood donor and a Big Brother for decades. Volunteering for research is a way to help society get the upper hand on Alzheimer’s disease, he said, and the huge suffering and costs that it brings.

    “We’re living longer and we understand what makes our bodies live longer,” said Wolff, who turns 70 in September. “If this is something that they don’t conquer, people are not going to have a quality of life at the end.”

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition
    Welcome to Brown

    Brown U Robinson Hall
    Located in historic Providence, Rhode Island and founded in 1764, Brown University is the seventh-oldest college in the United States. Brown is an independent, coeducational Ivy League institution comprising undergraduate and graduate programs, plus the Alpert Medical School, School of Public Health, School of Engineering, and the School of Professional Studies.

    With its talented and motivated student body and accomplished faculty, Brown is a leading research university that maintains a particular commitment to exceptional undergraduate instruction.

    Brown’s vibrant, diverse community consists of 6,000 undergraduates, 2,000 graduate students, 400 medical school students, more than 5,000 summer, visiting and online students, and nearly 700 faculty members. Brown students come from all 50 states and more than 100 countries.

    Undergraduates pursue bachelor’s degrees in more than 70 concentrations, ranging from Egyptology to cognitive neuroscience. Anything’s possible at Brown—the university’s commitment to undergraduate freedom means students must take responsibility as architects of their courses of study.

  • richardmitnick 10:34 am on January 11, 2017 Permalink | Reply
    Tags: A healthy lifestyle may help you sidestep Alzheimer’s, Alzheimer’s disease, , ,   

    From HMS: “A healthy lifestyle may help you sidestep Alzheimer’s” 

    Harvard University

    Harvard University

    Harvard Medical School

    Harvard Medical School

    January 09, 2017
    Heidi Godman

    No image caption. No image credit

    January is an inspiring time to make resolutions about eating a healthy diet and exercising more, maybe because you want to look or feel better. Personally, those reasons aren’t always enough to keep me from skipping a workout if I have too much on my schedule. I guess I’m a typical mom, putting my family and my job first.

    But this year, I have plenty of renewed inspiration to put my health first, and it’s the kind that will keep me up at night if I don’t stick to it: evidence suggests that adopting healthier lifestyle habits may help you thwart or even prevent the development of Alzheimer’s disease. Dementia runs in my family.

    About Alzheimer’s

    Alzheimer’s disease, the most common form of dementia, is characterized by the accumulation of two types of protein in the brain: tangles (tau) and plaques (amyloid-beta). Eventually, Alzheimer’s kills brain cells and takes people’s lives.

    What causes Alzheimer’s? We still aren’t sure. “For 1% of all cases, there are three genes that determine definitively whether you will have Alzheimer’s, and all three relate to amyloid-beta production, which in these cases is likely the cause of Alzheimer’s,” says Dr. Gad Marshall, associate medical director of clinical trials at the Center for Alzheimer Research and Treatment at Harvard-affiliated Brigham and Women’s Hospital. “For the other 99%, amyloid and tau are closely associated with Alzheimer’s, but many things may contribute to the development of symptoms, such as inflammation in the brain, vascular risk factors, and lifestyle.”

    Promising evidence

    So far, evidence suggests that several healthy habits may help ward off Alzheimer’s. Consider the following steps.

    Exercise. “The most convincing evidence is that physical exercise helps prevent the development of Alzheimer’s or slow the progression in people who have symptoms,” says Dr. Marshall. “The recommendation is 30 minutes of moderately vigorous aerobic exercise, three to four days per week.”

    Eat a Mediterranean diet. “This has been shown to help thwart Alzheimer’s or slow its progression. A recent study showed that even partial adherence to such a diet is better than nothing, which is relevant to people who may find it difficult to fully adhere to a new diet,” says Dr. Marshall. The diet includes fresh vegetables and fruits; whole grains; olive oil; nuts; legumes; fish; moderate amounts of poultry, eggs, and dairy; moderate amounts of red wine; and red meat only sparingly.

    Get enough sleep. “Growing evidence suggests that improved sleep can help prevent Alzheimer’s and is linked to greater amyloid clearance from the brain,” says Dr. Marshall. Aim for seven to eight hours per night.

    Not as certain

    We have some — but not enough — evidence that the following lifestyle choices help prevent Alzheimer’s.

    Learn new things. “We think that cognitively stimulating activities may be helpful in preventing Alzheimer’s, but the evidence for their benefit is often limited to improvement in a learned task, such as a thinking skills test, that does not generalize to overall improvement in thinking skills and activities of daily living,” says Dr. Marshall.

    Connect socially. “We think that greater social contact helps prevent Alzheimer’s,” explains Dr. Marshall, but so far, “there is only information from observational studies.”

    Drink — but just a little. There is conflicting evidence about the benefit of moderate alcohol intake (one drink per day for women, one or two for men) and reduced risk of Alzheimer’s. “It is thought that wine in particular, and not other forms of alcohol, may be helpful, but this has not been proved,” says Dr. Marshall.

    What you should do

    Even though we don’t have enough evidence that all healthy lifestyle choices prevent Alzheimer’s, we do know they can prevent other chronic problems. For example, limiting alcohol intake can help reduce the risk for certain cancers, such as breast cancer. So it’s wise to make as many healthy lifestyle choices as you can. “They’re all beneficial, and if they wind up helping you avoid Alzheimer’s, all the better,” says Dr. Marshall.

    But don’t feel like you need to rush into a ramped-up routine of living a healthier lifestyle. All it takes if one small change at a time, such as:

    exercising an extra day per week.
    getting rid of one unhealthy food from your diet.
    going to bed half an hour earlier, or shutting off electronic gadgets half an hour earlier than normal, to help you wind down.
    listening to a new kind of music, or listening to a podcast about a topic you’re unfamiliar with.
    or having lunch with a friend you haven’t seen in a while.

    Once you make one small change, try making another. Over time, they will add up. My change is that I’m going to add 15 more minutes to my exercise routine; that way, I’ll rack up more exercise minutes per week, and I won’t feel bad if I have to skip a workout now and then. By putting my health first, I’ll be in better shape for my family and my job, and hopefully, I’ll be better off in older age.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    HMS campus

    Established in 1782, Harvard Medical School began with a handful of students and a faculty of three. The first classes were held in Harvard Hall in Cambridge, long before the school’s iconic quadrangle was built in Boston. With each passing decade, the school’s faculty and trainees amassed knowledge and influence, shaping medicine in the United States and beyond. Some community members—and their accomplishments—have assumed the status of legend. We invite you to access the following resources to explore Harvard Medical School’s rich history.

    Harvard University campus

    Harvard is the oldest institution of higher education in the United States, established in 1636 by vote of the Great and General Court of the Massachusetts Bay Colony. It was named after the College’s first benefactor, the young minister John Harvard of Charlestown, who upon his death in 1638 left his library and half his estate to the institution. A statue of John Harvard stands today in front of University Hall in Harvard Yard, and is perhaps the University’s best known landmark.

    Harvard University has 12 degree-granting Schools in addition to the Radcliffe Institute for Advanced Study. The University has grown from nine students with a single master to an enrollment of more than 20,000 degree candidates including undergraduate, graduate, and professional students. There are more than 360,000 living alumni in the U.S. and over 190 other countries.

  • richardmitnick 1:35 pm on January 6, 2017 Permalink | Reply
    Tags: Alzheimer’s disease, , , Researchers identify different 'types' of Alzheimer’s based on protein clumps in the brain,   

    From Science Alert: “Researchers identify different ‘types’ of Alzheimer’s based on protein clumps in the brain” 


    Science Alert

    4 JAN 2017

    Juan Gaertner/Shutterstock

    Alzheimer’s isn’t just one disease.

    An international team of researchers has found evidence that the specific type of protein clumps in a person’s brain might help identify different ‘types’ of Alzheimer’s disease.

    These findings might help future researchers and doctors accurately identify different subtypes of the disease, making treatments and diagnostic practices more specialised, pushing us one step closer to conquering Alzheimer’s.

    While you might not have heard of different ‘types’ of Alzheimer’s before, researchers have previously found that the disease – which was once thought of as one single ailment – operates differently based on what subtype of the disease a person has.

    In short, there are three known types of Alzheimer’s: typical Alzheimer’s, posterior cortical atrophy Alzheimer’s, and rapidly progressive Alzheimer’s.

    “Because the presentation varies from person to person, there has been suspicion for years that Alzheimer’s represents more than one illness,” said Dale Bredesen, from the University of California, Los Angeles, who was not involved in the new study but did earlier work to identify the three subtypes.

    “The important implications of this are that the optimal treatment may be different for each group, there may be different causes, and, for future clinical trials, it may be helpful to study specific groups separately.”

    Earlier studies like the one Bredesen was involved with suggested that these subtypes might reveal themselves in how amyloid-beta peptides self-assemble into protein fibres known as fibrils in the brains of those with Alzheimer’s.

    Now, a team of researchers working with the National Institutes of Health (NIH) in the US and other agencies have found that these fibrils – which you can think of as ‘protein clumps’ – do, in fact, correlate with the different subtypes of the disease.

    To come to that conclusion, the team – led by Robert Tycko, from the NIH – analysed the fibrils inside 37 different tissue samples from 18 individuals with each individual having one of the three subtypes of Alzheimer’s.

    When complete, the team found that the fibrils housed inside the tissue samples had a specific structure for those with typical Alzheimer’s and posterior cortical atrophy, meaning that the presence of these structures could be a go-to indicator of these two types.

    Those suffering from the rapidly progressive form of the disease, on the other hand, had a multitude of fibril structures, making it a lot harder to identify because there wasn’t one specific structure belonging to it.

    What these findings suggest is that doctors might be able to analyse tissue samples from patients who have been diagnosed with Alzheimer’s to accurately judge which subtype of the disease they have.

    That would mean they could then potentially administer a more suitable treatment for that specific type, offering new hope to those suffering from the disease.

    Also, understanding how the three subtypes differ could lead to better, more specific treatments that can help us push forward to finding a cure for the disease in general.

    “A better understanding of the neurotoxic amyloid-beta aggregates and of correlations between their structure and disease subtypes might help the development of new diagnostic tests and treatments for Alzheimer’s disease,” the team said.

    It’s important to note, though, that the sample size used for the recent study was quite small, with the team only analysing tissue from 18 individuals. It will take a more comprehensive pool of data before any conclusions can be drawn, though this is definitely a good first step.

    In the US alone, about 5.4 million people suffer from Alzheimer’s, costing individuals and families up to US$5,000 per year for care and costing the economy at large a whopping $236 billion per year. Finding a cure, or at least better treatments, is a major pursuit for scientists across the globe.

    The team’s work was published in Nature.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

  • richardmitnick 9:30 am on December 28, 2016 Permalink | Reply
    Tags: Alzheimer’s disease, , ,   

    From Vanderbilt: “Investigational new drug for Alzheimer’s scheduled for first study in humans” 

    Vanderbilt U Bloc

    Vanderbilt University

    Dec. 27, 2016
    Bill Snyder

    Vanderbilt University scientists have received notification from the U.S. Food and Drug Administration (FDA) that testing in humans may proceed for an investigational new drug for Alzheimer’s disease after more than 10 years of research by scientists at Vanderbilt University and Vanderbilt University Medical Center.

    It is relatively uncharted territory for an academic drug discovery group to take a molecule from the laboratory setting to the clinical trials stage.

    “The movement to the clinical phase of the research is the result of tireless colleagues reaching across disciplines in pursuit of the shared goal of hoping to someday improve the lives of individuals with Alzheimer’s disease and possibly other brain disorders, such as schizophrenia,” said Provost and Vice Chancellor for Academic Affairs Susan R. Wente, Ph.D. “This work exactly illustrates the critical role that basic science conducted in partnership with a world-class medical center can play in advancing knowledge in an attempt to fight a devastating disease.”

    For Alzheimer’s disease, the aim is for the investigational drug to target major pathologies of the disease and selectively activate a key receptor in the brain. The Vanderbilt researchers believe that the current standard of care for Alzheimer’s disease, cholinesterase inhibitors, has a different mechanism of action. They are hoping to establish through future clinical testing that the molecule is broadly effective across a number of cognitive and neuropsychiatric disorders, including schizophrenia.

    P. Jeffrey Conn, Ph.D.

    “This is the first instance I am aware of where an academic drug discovery group moved a molecule designed to hopefully treat a chronic brain disorder all the way from early discovery to human trials without there being, at some point along the way, a pharmaceutical partner,” said P. Jeffrey Conn, Ph.D., Lee E. Limbird Professor of Pharmacology in the Vanderbilt University School of Medicine and director of the Vanderbilt Center for Neuroscience Drug Discovery (VCNDD).

    “And that really is crossing what people refer to all of the time as the ‘Valley of Death,’ where good research discoveries have a hard time moving into the clinical testing phase due to lack of funding,” he said. “Importantly, at this early stage, the FDA has only granted permission to assess potential safety of this investigational new drug in healthy volunteers” said Conn. “We cannot predict the outcome, but if these studies are successful in demonstrating that the investigational drug can be safely administered to humans, this would pave the way to allow filing of additional applications with the FDA to seek permission to advance to testing for efficacy in improving cognitive function in patients suffering from Alzheimer’s disease, and possibly schizophrenia or other brain disorders. While we cannot predict the outcome of any future safety or efficacy studies, this decision by FDA allowing clinical research to begin represents a major milestone in allowing us to hopefully provide answers to those critical questions in the future.”

    Craig W. Lindsley, Ph.D.

    VCNDD Co-Director Craig W. Lindsley, Ph.D., director of Medicinal Chemistry and William K. Warren, Jr. Professor of Medicine, said Phase I testing will assess drug safety and tolerability in healthy volunteer participants, a process that could take a year. If successful, the Phase II and III studies would include efficacy assessments in patients with Alzheimer’s disease and could take three to five years to complete.

    “We are hoping to address what we see as an unmet medical need,” Lindsley said. “For Alzheimer’s patients, the standard of care for symptomatic treatment remains cholinesterase inhibitors, which are 25 years old at this point. There hasn’t been any real scientific advancement in this field in a long time.”

    Lindsley and Conn credit The William K. Warren Foundation for its philanthropic investments along the way to make clinical trials for this investigational drug a reality.

    “One of the most challenging things about doing this in an academic environment is funding,” Lindsley said. “Every step requires funding and if there is a delay or break in funding, then everything sits idle and potentially innovative approaches for patient care do not advance.”

    “Being matched with the Warrens happened serendipitously. They have invested so much in our programs, and it is wonderful to show them progress on their investments,” he said. “Without the financial support from the Warrens, this investigational drug would not be poised to enter human clinical trials.”

    The William K. Warren Foundation Chief Executive Officer John-Kelly Warren said he is gratified that FDA has allowed for the investigational drug to proceed to testing in human beings.

    “Although this is an important sequential milestone, the only milestone that matters to us is the hope that one day we will learn that this investigational new drug has positively and safely changed the life of a patient suffering from a brain disorder such as schizophrenia or Alzheimer’s disease,” Warren said.

    “That day will warrant a celebration felt in the heavens. Until then, we are prepared to support the VCNDD research team until they can deliver the necessary results,” he said.

    A NIH National Cooperative Drug Discovery/Development grant funded the early basic science and discovery of this investigational drug and the Alzheimer’s Drug Discovery Foundation and Harrington Discovery Institute helped support some of the key toxicity studies that FDA required, Conn said.

    “The investigational new drug has the potential to improve cognitive functions with fewer unwanted side effects. This could someday be an important advance for the treatment of cognitive deficits in psychiatric disorders and Alzheimer’s disease,” said Joshua Gordon, M.D., Ph.D., director of the National Institute of Mental Health, which co-funded the research.

    Conn and Lindsley said Vanderbilt’s “team science” approach included contributions from the director of Translational Pharmacology and Development for the VCNDD and Assistant Professor Carrie K. Jones, Ph.D., who coordinated the IND drafting, submission, and subsequent development into Phase I, director of Molecular Pharmacology for the VCNDD and Research Associate Professor of Pharmacology Colleen Niswender, Ph.D., for the molecular pharmacology; Research Assistant Professor of Pharmacology Jerri Rook, Ph.D., for the behavioral studies; and Research Assistant Professor of Pharmacology Thomas Bridges, Ph.D., and Research Assistant Professor of Pharmacology Anna Blobaum, Ph.D., for drug metabolism and pharmacokinetic profiling.

    Paul Newhouse, M.D., director of the Center for Cognitive Medicine at VUMC and Jim Turner Professor in Cognitive Disorders, is expected to lead the upcoming clinical study funded in part by the Alzheimer’s Association and Alzheimer’s Drug Discovery Foundation.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Vanderbilt Campus

  • richardmitnick 12:59 pm on September 12, 2016 Permalink | Reply
    Tags: Alzheimer’s disease, , ,   

    From MSU: “Alzheimer’s beginnings prove to be a sticky situation” 

    Michigan State Bloc

    Michigan State University

    Sept. 12, 2016
    Layne Cameron
    Lisa Lapidus

    MSU’s Lisa Lapidus uses laser technology to reveal a common trait of Alzheimer’s disease – a sticky situation that could lead to new targets for medicinal treatments. Photo by G.L. Kohuth

    Laser technology has revealed a common trait of Alzheimer’s disease – a sticky situation that could lead to new targets for medicinal treatments.

    Alzheimer’s statistics are always staggering. The neurodegenerative disease affects an estimated 5 million Americans, one in three seniors dies with Alzheimer’s or a form of dementia, it claims more lives than breast and prostate cancers combined, and its incidence is rising.

    To help fight this deadly disease, Lisa Lapidus, Michigan State University professor of physics and astronomy, has found that peptides, or strings of amino acids, related to Alzheimer’s wiggle at dangerous speeds prior to clumping or forming the plaques commonly associated with Alzheimer’s.

    “Strings of 40 amino acids are the ones most-commonly found in healthy individuals, but strings of 42 are much more likely to clump,” said Lapidus, who published the results in the current issue of ChemPhysChem. “We found that the peptides’ wiggle speeds, the step before aggregation, was five times slower for the longer strings, which leaves plenty of time to stick together rather than wiggle out of the way.”

    This so-called “wiggle” precedes clumping, or aggregating, which is the first step of neurological disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease. Lapidus pioneered the use of lasers to study the speed of protein reconfiguration before aggregation.

    If reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow. If reconfiguration is the same speed, however, aggregation is fast. She calls the telltale wiggle that she discovered the “dangerous middle.”

    “The dangerous middle is the speed in which clumping happens fastest,” Lapidus said. “But we were able to identify some ways that we can bump that speed into a safer zone.”

    Lapidus and her team of MSU scientists, including Srabasti Acharya (now a biotechnology researcher in the San Francisico Bay area), Kinshuk Srivastava and Suresh Babu Nagarajan, found that increasing pH levels kept the amino acids wiggling at fast, safe speeds. Also, a naturally occurring molecule, curcumin (from the spice turmeric), kept the peptide out of the dangerous middle.

    While this is not a viable drug candidate because it does not easily cross the blood-brain barrier, the filter that controls what chemicals reach the brain, they do provide strong leads that could lead to medicinal breakthroughs.

    Along with new drug targets, Lapidus’ research provides a potential model of early detection. By the time patients show symptoms and go to a doctor, aggregation already has a stronghold in their brains. Policing amino acids for wiggling at dangerous speeds could tip off doctors long before the patient begins to suffer from the disease.

    This research was funded by the National Institutes of Health.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Michigan State Campus

    Michigan State University (MSU) is a public research university located in East Lansing, Michigan, United States. MSU was founded in 1855 and became the nation’s first land-grant institution under the Morrill Act of 1862, serving as a model for future land-grant universities.

    MSU pioneered the studies of packaging, hospitality business, plant biology, supply chain management, and telecommunication. U.S. News & World Report ranks several MSU graduate programs in the nation’s top 10, including industrial and organizational psychology, osteopathic medicine, and veterinary medicine, and identifies its graduate programs in elementary education, secondary education, and nuclear physics as the best in the country. MSU has been labeled one of the “Public Ivies,” a publicly funded university considered as providing a quality of education comparable to those of the Ivy League.

    Following the introduction of the Morrill Act, the college became coeducational and expanded its curriculum beyond agriculture. Today, MSU is the seventh-largest university in the United States (in terms of enrollment), with over 49,000 students and 2,950 faculty members. There are approximately 532,000 living MSU alumni worldwide.

  • richardmitnick 7:06 am on September 8, 2016 Permalink | Reply
    Tags: Alzheimer’s disease, , ,   

    From U Texas at Austin: “Chemists Garner New Insights into Protein Linked to Alzheimer’s Disease” 

    U Texas Austin bloc

    University of Texas at Austin

    07 September 2016
    Christine S Sinatra, Chemistry

    Alzheimer’s disease, the sixth leading cause of death in the United States, has proven especially thorny for researchers: no cure has been found, nor has there been any treatment proven to slow the progression of the disease once it sets in. In a new study published in the Proceedings of the National Academy of Sciences, scientists have taken a back-to-the-beginning approach, examining what happens at the start of a chain reaction that occurs before onset of the disease.

    Amyloid plaques in a brain tissue sample. Credit: CDC/ Teresa Hammett.

    Dave Thirumalai, a theoretical chemist at The University of Texas at Austin and chair of the Department of Chemistry, and John Straub, a computational chemist at Boston University, teamed up to understand how a mutation in a normal protein can create amyloid β, a key contributor to Alzheimer’s disease. Amyloid β builds up as a plaque in the brains of people with the disease, apparently leading to dementia and other symptoms.

    Amyloid β occurs when a protein found in healthy brains – called the amyloid precursor protein – gets cut by an enzyme in a particular way. Thirumalai and the other researchers wanted to understand what interactions were occurring in the membrane, and under which circumstances, to cause the precursor to be severed in such a way that it mutates into amyloid β.

    “Several enzymes cut this amyloid precursor protein, which is a very long protein spanning the membrane and outside the membrane,” Thirumalai said. “Some products of cutting it are benign, some are not. One can lead to Alzheimer’s disease.”

    The scientific team has spent several years examining how circumstances in the membrane can trigger the disease-causing mutation in the precursor protein. In the latest study, Thirumalai and colleagues report that variations in the membrane, as well as in the structure of the protein, can interact in ways that lead to production of amyloid β. Drug developers could potentially use insights from such studies to understand a new way to prevent the onset of the disease.

    Thirumalai and the other scientists plan to continue this line of exploration, including looking into how cholesterol affects the interactions between the membrane, the precursor protein, and the enzyme each time the disease-causing mutation occurs.

    “In order to devise a therapy against this process, you need to understand the life cycle of the amyloid precursor protein and figure out what it is doing and what the membrane is doing,” Thirumalai says. “These promising leads and new research that we and many others are exploring will hopefully in the end give us a better target for therapy. I’m cautiously optimistic about that.”

    The group’s research was funded with a grant from the National Institutes of Health.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    U Texas Arlington Campus

    In 1839, the Congress of the Republic of Texas ordered that a site be set aside to meet the state’s higher education needs. After a series of delays over the next several decades, the state legislature reinvigorated the project in 1876, calling for the establishment of a “university of the first class.” Austin was selected as the site for the new university in 1881, and construction began on the original Main Building in November 1882. Less than one year later, on Sept. 15, 1883, The University of Texas at Austin opened with one building, eight professors, one proctor, and 221 students — and a mission to change the world. Today, UT Austin is a world-renowned higher education, research, and public service institution serving more than 51,000 students annually through 18 top-ranked colleges and schools.

  • richardmitnick 6:40 am on September 1, 2016 Permalink | Reply
    Tags: Aducanumab drug trial, Alzheimer’s disease, , ,   

    From COSMOS: “Drug scrubs toxic clumps from Alzheimer’s brains” 

    Cosmos Magazine bloc


    01 September 2016
    Belinda Smith

    A computer illustration of a healthy brain cell (left), one with amyloid clumps (yellow, centre), and a dead cell being digested by microglia cells (red, right). New research in human brains show the drug aducanumab can clear away these amyloid clumps. JUAN GAERTNER / SCIENCE PHOTO LIBRARY / Getty Images

    Aducanumab breaks down the harmful protein plaques that are thought to cause the neurodegenerative disease, but there’s still a long way to go before it’s found on the pharmacist’s shelf.

    A drug has been shown effective in clearing away toxic proteins in human brains thought to cause Alzheimer’s disease, a new study shows.

    But, researchers warn, there’s more work needed before the drug, called aducanumab, moves into the clinic – if it ever does.

    The work, published in Nature, is “tantalising, but not definitive”, says University College London neuroscientist John Hardy.

    Alzheimer’s disease is a common neurodegenerative disorder among older folk. One in nine people over the age of 65 years has the disease.

    Outwardly, symptoms include memory loss, confusion, dementia and mood changes. But the changes that occur within the brain are much sneakier, often accumulating for decades before any cognitive or emotional symptoms emerge.

    One of the main culprits is beta amyloid protein. Everyone has a little beta amyloid in their brain, but in Alzheimer’s disease it amasses as insoluble clumps – particularly in the hippocampus, the brain structure responsible for learning and memory.

    Cells surrounding these clumps shrink and die.

    But treatment isn’t as easy as scooping out the plaques. The brain’s first line of defence is the blood-brain barrier – a network of tightly packed cells that line blood vessels.

    So the challenge has been to find a drug that can pierce the blood-brain barrier, hunt down amyloid clumps and dismantle them for the brain’s own immune cells, called microglia, to dispose of.

    A recent promising candidate was aducanumab. It can breach the blood-brain barrier and it selectively binds to amyloid aggregates – can it help clear them away too?

    Boston-based pharmaceutical company Biogen and scientists from the US and Switzerland administered aducanumab to mice genetically engineered to over-produce amyloid. They found the drug bound to and shrank amyloid clumps in the mouse brain.

    It was a good start. But mice and humans, while similar in many ways, are very different in others. Could it work in people too – and could the dose affect how well it performed?

    The team recruited 165 patients diagnosed with mild Alzheimer’s disease and randomly allocated them to one of four groups: a placebo group or one of three treatment groups that would receive monthly intravenous aducanumab for a year.

    The first treatment group was injected with three milligrams of aducanumab per kilogram of weight, the second received six milligrams per kilogram and the final, 10 milligrams per kilogram.

    Before beginning treatment (or placebo – patients weren’t told which group they were in) their brain was scanned using a technique called florbetapir PET, which detects brain amyloid levels.

    While this all sounds fantastic, the team admits the work has a number of limitations.

    As expected, all brains contained high levels of beta amyloid. After a year of treatment or placebo, they were scanned again.

    Those taking the placebo saw no change in brain amyloid levels. (No less, but no more either. This suggests the participants reached amyloid brain saturation before the trial began.)

    The aducanumab groups, though, had much of their amyloid cleared away. The effect was dose-dependent too, with those on the highest dose receiving the most benefits.

    While this all sounds fantastic, the team admits the work has a number of limitations.

    The initial cohort of 165 – which was from the US only – was whittled down to 125 over the course of the year. Some 20 participants experienced side effects such as headaches and dropped out.

    The researchers didn’t measure, to a great extent, how well the patients did cognitively after treatment either.

    A couple of tests showed a trend of slowing cognitive decline in the aducanumab-taking patients, but it was not definitive.

    “The good news is that by scanning patient brains the researchers show the drug is doing its job in reducing amyloid beta levels within the brain,” says Mark Dallas, a neuroscientist at the University of Reading in the UK.

    “However, because of the study design, it cannot tell us if there is any improvement in brain function of those that received the drug.”

    And while aducanumab targets beta amyloid, it ignores another aspect of Alzheimer’s pathology, tau aggregates.

    Tau proteins, which form part of a cell’s interior transport system, warp with the disease. These tau tangles disrupt a cell’s functioning and it eventually dies.

    Still, more clinical trials will elucidate aducanumab’s cognitive effects. It might be that clearing amyloid is enough to give patients a few more years of clear thinking.

    Indeed, the researchers write, phase 3 testing is in development. Statistically, the odds are stacked against them – only 0.4% of Alzheimer’s drugs make it past phase 3 trials. Only time will tell.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

  • richardmitnick 1:26 pm on August 11, 2016 Permalink | Reply
    Tags: Alzheimer’s disease, , , ,   

    From U Cambridge: “Gene signature in healthy brains pinpoints the origins of Alzheimer’s disease” 

    U Cambridge bloc

    Cambridge University

    10 Aug 2016
    Sarah Collins

    In healthy tissues, a gene expression signature associated with amyloid-beta and tau aggregation echoes the progression of AD well before the onset of the disease. Credit: J. Freer

    A specific gene expression pattern maps out which parts of the brain are most vulnerable to Alzheimer’s disease, decades before symptoms appear, and helps define the molecular origins of the disease.

    Researchers have discovered a gene signature in healthy brains that echoes the pattern in which Alzheimer’s disease spreads through the brain much later in life. The findings, published in the journal Science Advances, could help uncover the molecular origins of this devastating disease, and may be used to develop preventative treatments for at-risk individuals to be taken well before symptoms appear.

    The results, by researchers from the University of Cambridge, identified a specific signature of a group of genes in the regions of the brain which are most vulnerable to Alzheimer’s disease. They found that these parts of the brain are vulnerable because the body’s defence mechanisms against the proteins partly responsible for Alzheimer’s disease are weaker in these areas.

    Healthy individuals with this specific gene signature are highly likely to develop Alzheimer’s disease in later life, and would most benefit from preventative treatments, if and when they are developed for human use.

    Alzheimer’s disease, the most common form of dementia, is characterised by the progressive degeneration of the brain. Not only is the disease currently incurable, but its molecular origins are still unknown. Degeneration in Alzheimer’s disease follows a characteristic pattern: starting from the entorhinal region and spreading out to all neocortical areas. What researchers have long wondered is why certain parts of the brain are more vulnerable to Alzheimer’s disease than others.

    “To answer this question, what we’ve tried to do is to predict disease progression starting from healthy brains,” said senior author Professor Michele Vendruscolo of the Centre for Misfolding Diseases at Cambridge’s Department of Chemistry. “If we can predict where and when neuronal damage will occur, then we will understand why certain brain tissues are vulnerable, and get a glimpse at the molecular origins of Alzheimer’s disease.”

    One of the hallmarks of Alzheimer’s disease is the build-up of protein deposits, known as plaques and tangles, in the brains of affected individuals. These deposits, which accumulate when naturally-occurring proteins in the body fold into the wrong shape and stick together, are formed primarily of two proteins: amyloid-beta and tau.

    “We wanted to know whether there is something special about the way these proteins behave in vulnerable brain tissue in young individuals, long before the typical age of onset of the disease,” said Vendruscolo.

    Vendruscolo and his colleagues found that part of the answer lay within the mechanism of control of amyloid-beta and tau. Through the analysis of more than 500 samples of healthy brain tissues from the Allen Brain Atlas, they identified a signature of a group of genes in healthy brains. When compared with tissue from Alzheimer’s patients, the researchers found that this same pattern is repeated in the way the disease spreads in the brain.

    “Vulnerability to Alzheimer’s disease isn’t dictated by abnormal levels of the aggregation-prone proteins that form the characteristic deposits in disease, but rather by the weaker control of these proteins in the specific brain tissues that first succumb to the disease,” said Vendruscolo.

    Our body has a number of effective defence mechanisms which protect it against protein aggregation, but as we age, these defences get weaker, which is why Alzheimer’s generally occurs in later life. As these defence mechanisms, collectively known as protein homeostasis systems, get progressively impaired with age, proteins are able to form more and more aggregates, starting from the tissues where protein homeostasis is not so strong in the first place.

    Earlier this year, the same researchers behind the current study identified a possible ‘neurostatin’ that could be taken by healthy individuals in order to slow or stop the progression of Alzheimer’s disease, in a similar way to how statins are taken to prevent heart disease. The current results suggest a way to exploit the gene signature to identify those individuals most at risk and who would most benefit from taking a neurostatin in earlier life.

    Although a neurostatin for human use is still quite some time away, a shorter-term benefit of these results may be the development of more effective animal models for the study of Alzheimer’s disease. Since the molecular origins of the disease have been unknown to date, it has been difficult to breed genetically modified mice or other animals that repeat the full pathology of Alzheimer’s disease, which is the most common way for scientists to understand this or any disease in order to develop new treatments.

    “It is exciting to consider that the molecular origins identified here for Alzheimer’s may predict vulnerability for other diseases associated with aberrant aggregation – such as ALS, Parkinson’s and frontotemporal dementia,” said Rosie Freer, a PhD student in the Department of Chemistry and the study’s lead author. “I hope that these results will help drug discovery efforts – that by illuminating the origin of disease vulnerability, there will be a clearer target for those working to cure Alzheimer’s.”

    “The results of this particular study provide a clear link between the key factors that we have identified as underlying the aggregation phenomenon and the order in which the effects of Alzheimer’s disease are known to spread through the different regions of the brain,” said study co-author Professor Christopher Dobson, who is Master of St John’s College, Cambridge. “Linking the properties of specific protein molecules to the onset and spread of neuronal damage is a crucial step in the quest to find effective drugs to combat this dreadful neurodegenerative condition, and potentially other diseases related to protein misfolding and aggregation.”

    Addressing these problems represents the core programme of research of the Centre for Misfolding Diseases, which is directed by Chris Dobson, Tuomas Knowles and Michele Vendruscolo. The primary mission of the Centre is to develop a fundamental understanding of the molecular origins of the variety of disorders associated with the misfolding and aggregation of proteins, which include Parkinson’s disease, ALS and type II diabetes as well as Alzheimer’s disease, and then to use such understanding for the rational design of novel therapeutic strategies.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    U Cambridge Campus

    The University of Cambridge (abbreviated as Cantab in post-nominal letters) is a collegiate public research university in Cambridge, England. Founded in 1209, Cambridge is the second-oldest university in the English-speaking world and the world’s fourth-oldest surviving university. It grew out of an association of scholars who left the University of Oxford after a dispute with townsfolk. The two ancient universities share many common features and are often jointly referred to as “Oxbridge”.

    Cambridge is formed from a variety of institutions which include 31 constituent colleges and over 100 academic departments organised into six schools. The university occupies buildings throughout the town, many of which are of historical importance. The colleges are self-governing institutions founded as integral parts of the university. In the year ended 31 July 2014, the university had a total income of £1.51 billion, of which £371 million was from research grants and contracts. The central university and colleges have a combined endowment of around £4.9 billion, the largest of any university outside the United States. Cambridge is a member of many associations and forms part of the “golden triangle” of leading English universities and Cambridge University Health Partners, an academic health science centre. The university is closely linked with the development of the high-tech business cluster known as “Silicon Fen”.

Compose new post
Next post/Next comment
Previous post/Previous comment
Show/Hide comments
Go to top
Go to login
Show/Hide help
shift + esc
%d bloggers like this: