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“Wakefulness” Part of the Brain Attacked First in Alzheimer’s, Study Says

Lea Grinberg, a neuropathologist and associate professor at the UCSF Memory and Aging Center in San Francisco’s Mission Bay, holds slides of brain tissue used for research on August 15, 2019. (Lindsey Moore/KQED)

People who donate their bodies to science might never have dreamed what information lies deep within their brains.

Even when that information has to do with sleep.

Scientists used to believe that people who napped a lot were at risk for developing Alzheimer’s disease. But Lea Grinberg with the UCSF Memory and Aging Center started to wonder if “risk” was too light a term — what if, instead, napping indicated an early stage of Alzheimer’s?

About a decade ago, Grinberg — a neuropathologist and associate professor — was working with her team to map a protein called tau in donated brains. Some of their data, published last week, revealed drastic differences between healthy brains and those from Alzheimer’s patients in the parts of the brain responsible for wakefulness.

Lea Grinberg uses a program that takes a microscope’s magnification of brain tissue on a slide and projects it on a computer screen on August 15, 2019. The different colors represent different biological features in the brain tissue sample, including neurons and tau protein. (Lindsey Moore/KQED)

Wakefulness centers in the brain showed the buildup of tau — a protein that clogs neurons, Grinberg says, and lets debris accumulate. Gradually, these clogged neurons die. Some areas of the diseased brains had lost as much as 75% of their neurons. That may have led to the excessive napping scientists had observed before. Although the team only studied brains from 13 Alzheimer’s patients and 7 healthy individuals, Grinberg says that the degeneration caused by Alzheimer’s was so profound they were sure of its significance.

“We are kind of changing our understanding of what Alzheimer’s disease is,” she says. “It’s not only a memory problem, but it’s a problem in the brain that causes many other symptoms.”

Although these symptoms aren’t as severe as complete loss of memory or motor functions, Grinberg says they can still hold real consequences for a person’s quality of life. “Because if you don’t sleep well every day and if you… are not in the mood to do things like you were before, it’s very disappointing, right? My grandparents were like this.”

Grinberg says it’s important to know whether napping could be an early sign of Alzheimer’s, for treating symptoms and developing drugs that could slow the progression of the disease. Although there are no prescription drugs available to treat tau buildup, she says, a few are in clinical trials.

Lea Grinberg holds boxes filled with samples of brain tissue for study on August 15, 2019. (Lindsey Moore/KQED)

A public health professor and neuroscientist at UC Berkeley says the new information offers hope to researchers. William Jagust, who has studied Alzheimer’s for over 30 years, says the results could help select patients for clinical trials of new drugs that require early treatment. “It’s also just very important for understanding the evolution of Alzheimer’s disease with the hope that we eventually will have a drug,” he adds.

It’ll be awhile before doctors can diagnose anyone with Alzheimer’s based on how often they doze off. “There’s no practical application of this to clinical medicine as of today,” Jagust says, “but I think it’s on the cutting edge of the very, very important questions.”

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Source: “Wakefulness” Part of the Brain Attacked First in Alzheimer’s, Study Says

What is Alzheimer’s disease? Alzeimer’s (Alzheimer) disease is a neurodegenerative disease that leads to symptoms of dementia. Progression of Alzheimer’s disease is thought to involve an accumulation of beta-amyloid plaque and neurofibrillary tangles in the brain. Find more videos at http://osms.it/more. Study better with Osmosis Prime. Retain more of what you’re learning, gain a deeper understanding of key concepts, and feel more prepared for your courses and exams. Sign up for a free trial at http://osms.it/more. Subscribe to our Youtube channel at http://osms.it/subscribe. Get early access to our upcoming video releases, practice questions, giveaways and more when you follow us on social: Facebook: http://osms.it/facebook Twitter: http://osms.it/twitter Instagram: http://osms.it/instagram Osmosis’s Vision: Empowering the world’s caregivers with the best learning experience possible.

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How Will The Failure Of Biogen’s Alzheimer’s Drug, Aducanumab, Impact R&D?

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Photographer: Scott Eisen/Bloomberg

© 2016 Bloomberg Finance LP

The landscape of experimental Alzheimer’s disease (AD) drugs is strewn with failures, so much so that it has been referred to as “an unrelenting disaster zone”. Recognizing the greatly increasing number of patients with this disease, many biopharma companies have invested a lot of resources in attacking this problem, only to be turned away in late stage studies as happened to Merck with its BACE inhibitor, verubecestat, and Lilly with its beta-amyloid antibody, solanezumab.

Now add Biogen to the list of companies that have failed in this arena. Its drug, aducanumab, partnered with Eisai, was believed to be better in removing beta-amyloid from the brain than any agent previously tested. Many have hypothesized that beta-amyloid causes the formation of damaging clumps of debris in the brain leading to AD. Unfortunately, Biogen halted a major clinical trial with aducanumab due to a futility analysis showing that the drug doesn’t work.

This is a terrible result for Alzheimer’s patients who had hoped that this was the drug that would finally succeed in treating AD. But the demise of aducanumab is also disastrous for Biogen which had expended an enormous amount of resources into this program, likely at the expense of other opportunities. It was a risky bet and one for which Wall Street has delivered a punishing blow. Biogen’s stock dropped by nearly 30% shortly after announcing the disappointing aducanumab results.

How is Biogen going to respond? As John Carroll has reported, many industry analysts believe that there aren’t many gems in the Biogen pipeline that can make up for the loss of this potential blockbuster. In predicting Biogen’s next steps, perhaps there are some learnings from another such pipeline failure – that of Pfizer’s torcetrapib.

Torcetrapib was the first of a class of compounds known as CETP inhibitors, drugs that both raised HDL-cholesterol and lowered LDL-cholesterol. A CETP inhibitor had the potential to remodel a heart patient’s lipid profile thereby greatly reducing his risk of a heart attack or stroke. There was tremendous excitement generated in this potential breakthrough treatment, not just in Pfizer but also among cardiologists and heart patients. In fact, internal commercial analyses predicted annual sales in excess of $15 billion. However, as happened with aducanumab, on December 4th, 2006, Pfizer announced that torcetrapib failed its long-term clinical study. The drug was dead. The Wall Street reaction was swift, albeit not as dramatic as Biogen’s experience. Pfizer stock dropped 10% as a result of this news.

Internally, the Pfizer reaction was intense. Torcetrapib was supposed to be the blockbuster that would drive growth into the next decade. Its loss created an enormous hole. Pfizer CEO Jeff Kindler responded in a couple of ways. First, he decided to “right size” R&D in relation to lower expected future revenues. In effect, hundreds of millions of dollars needed to be cut from R&D. Pfizer’s R&D budget had already undergone major portfolio adjustments and reorganizations over the previous five years due to the acquisition of Warner-Lambert Parke-Davis in 2000 followed by the acquisition of Pharmacia in 2004. Meeting the new R&D budget targets weren’t going to be achieved by simple cuts; rather, major research sites had to be closed and jobs had to be eliminated. Gone were R&D sites around the world including those in France, Japan and, most significantly, the iconic laboratory in Ann Arbor, Michigan.

But budget cuts weren’t going to be enough for Pfizer to meet its desired goals. The company began assessing major M&A opportunities and in 2009 it acquired Wyeth for $68 billion leading to yet another round of reorganizations and portfolio reshuffling. The ripple effect of the torcetrapib demise was felt by the entire company and lasted for a number of years.

So, how will Biogen respond? Undoubtedly, there will be budget cuts. In addition, perhaps Biogen will look at its R&D portfolio and give a higher priority to those programs that have the potential to deliver revenues in the short term. There might also be a push to drop programs deemed to be very risky or where the proof-of-concept requires long, expensive clinical trials. Finally, it wouldn’t be surprising to see Biogen become aggressive in their M&A activities. But make no mistake. The death of an important drug like aducanumab will have both a short and a long term effect on Biogen as a company and especially on R&D.

I was the president of Pfizer Global Research and Development in 2007 where I managed more than 13,000 scientists and professionals in the United States, Europe, and Asi…

Source: How Will The Failure Of Biogen’s Alzheimer’s Drug, Aducanumab, Impact R&D?

How An Outsider In Alzheimer’s Research Bucked The Prevailing Theory & Clawed For Validation – Sharon Begley

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Robert Moir was damned if he did and damned if he didn’t. The Massachusetts General Hospital neurobiologist had applied for government funding for his Alzheimer’s disease research and received wildly disparate comments from the scientists tapped to assess his proposal’s merits. It was an “unorthodox hypothesis” that might “fill flagrant knowledge gaps,” wrote one reviewer, but another said the planned work might add little “to what is currently known……..

Read more: https://www.statnews.com/2018/10/29/alzheimers-research-outsider-bucked-prevailing-theory/

 

 

 

Your kindly Donations would be so effective in order to fulfill our future research and endeavors – Thank you

There Is Mounting Evidence That Herpes Leads To Alzheimers – Ruth Itzhaki

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More than 30 million people worldwide suffer from Alzheimer’s disease – the most common form of dementia. Unfortunately, there is no cure, only drugs to ease the symptoms. However, my own research suggests a way to treat the disease. I have found the strongest evidence yet that the herpes virus is a cause of Alzheimer’s, suggesting that effective and safe antiviral drugs might be able to treat the disease. We might even be able to vaccinate our children against it……..

Read more: http://www.bbc.com/future/story/20181022-there-is-mounting-evidence-that-herpes-leads-to-alzheimers

 

 

 

 

Your kindly Donations would be so effective in order to fulfill our future research and endeavors – Thank you

Alzheimer’s These psychiatric symptoms may be an early sign – Catharine Paddock PhD

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Working with the Brazilian Biobank for Aging Studies (BBAS) at the University of São Paulo, investigators at the University of California in San Francisco (UCSF) studied results of postmortem brain tissue tests and compared them with psychiatric symptoms obtained from detailed interviews conducted with people who knew the deceased well, such as relatives and carers. They suggest that their study — a paper on which now features in the Journal of Alzheimer’s Disease — reveals that psychiatric symptoms are not the cause of Alzheimer’s, but more likely early indicators of the disease…….

Read more: https://www.medicalnewstoday.com/articles/323366.php

 

 

 

Your kindly Donations would be so effective in order to fulfill our future research and endeavors – Thank you

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