Is Everything We Think We Know About Alzheimer’s Disease Wrong?

Overview: Recent scandals in Alzheimer’s research and problems with drugs designed to help people with Alzheimer’s disease, but failing to produce sufficient results, have made researchers question the overwhelming focus on amyloid beta in the study of the Alzheimer’s disease. Alzheimer’s disease.

Source: University of Michigan

If you’ve been following the news of Alzheimer’s research in recent months, you may be wondering what else could go wrong.

First, a long-awaited new drug called Aduhelm received Food & Drug Administration approval, but the actual effect on patients was so small that insurance doesn’t cover it for most patients.

Subsequently, several other promising drugs in development by pharmaceutical companies were sidelined or showed less than impressive results in clinical trials.

And then a scandal broke: new evidence came to light in Science that researchers had faked images in a paper published 16 years ago — a paper other researchers had relied on and relied on while doing their own work.

And what do all these developments have to do with each other?

They are all bound to the molecule beta-amyloid, the plaque-forming sludge that swallows the outside of brain cells. The molecule that decades of research has focused on as a major factor in the disease and possible treatments to reverse it.

But in fact, scientists at the Michigan Alzheimer’s Disease Center and elsewhere have spent years looking beyond amyloid for answers to the roots of dementia and ways to prevent or treat it.

“It’s true that amyloid plays a role in the brain and dementia, but Alzheimer’s disease is complicated and involves much more than one molecule,” says Henry Paulson, MD, Ph.D., who leads the center and his own lab research at Michigan Medicine and his clinical care for dementia and other neurodegenerative diseases for decades.

The article in the center of the scandal has to do with a specific form of amyloid, AB*56, which has been put forward as an important “toxic oligomer” that encourages plaque formation.

But Paulson says he and many of his colleagues haven’t paid much attention to it in years because researchers haven’t been as successful in achieving the same results as the original researchers claimed.

“I’m more concerned about what this news might mean for the public perception of science than about our ability to make progress against this disease,” he says. The long delay in discovering the alleged forgery is not ideal, demonstrating the importance of scientists voting and publishing results, even if their experiments cannot prove another team’s claim.”

This kind of publication of “negative results” – articles that do not give good news about a potentially promising idea – is not always encouraged, because scientists have more reason to leave those results on the shelf and spend time writing articles about things that do. work.

But if no one knows that an attempt to reproduce a scientific discovery has failed, then other scientists could turn their wheels by turning into a dead end.

Paulson notes that it is still important to study the protein that is cut, or cleaved, to make different forms of beta-amyloid, and the consequences of that process.

But he’s not necessarily surprised by the failure of Aduhelm, the much-discussed drug approved last year, to produce a significant effect even in the patients it was tested with.

The drug is not available in Michigan Medicine’s clinics or hospitals, and Medicare will only cover the high costs for people who participate in clinical trials. Other drugs in the pipeline at drug companies targeting beta-amyloid need careful research before approval, he adds.

“We believe that much more attention should be paid to other factors and proteins underlying various forms of dementia, ranging from environmental factors to the immune system, to specific molecules such as tau, the other signature protein of Alzheimer’s disease. he explains. “In my opinion, Aduhelm’s story underscores the importance of continuing to seek other therapeutic targets in Alzheimer’s disease and related dementia.”

Targeting amyloid for treatments can be like trying to saddle up a horse that has already left the stable, he says — too much has happened in the disease process by the time the plaques begin to form for treatment to have a ​to make a difference.

Working upstream in the process and doing more with modern tools to understand the process by studying people in the early stages of amnesia could be more important.

That’s why the Michigan Alzheimer’s Disease Center is always looking for people to participate in studies that include everything from brain scans to surveys. Anyone who wants to participate can start the process by conducting an initial survey.

Alzheimer’s and other dementias are complicated diseases and likely result from multiple things going wrong in the brain over time, not one rogue molecule, Paulson explains. So we may need to treat patients with multiple treatments at once, targeting different aspects of their disease, just like cancer or HIV-positive patients get today.

But in fact, scientists at the Michigan Alzheimer’s Disease Center and elsewhere have spent years looking beyond amyloid for answers to the roots of dementia and ways to prevent or treat it. Image is in the public domain

But in the meantime, research has already shown another important upstream effect that many people may not realize, Paulson says.

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There is ample evidence that middle-aged and older adults who want to reduce their risk of dementia or delay its onset should focus on healthy habits such as sleep, diet, exercise, social engagement, and controlling blood pressure and cholesterol. The role of lifelong learning and learning – informal or formal – is also clear

“When you’re 70 years old, I can’t tell you to go back in time and eat healthier or go to school for more years, but I can tell you that you need to do more to get a good experience as often as possible. get a good night’s sleep, and socialize with other people,” says Paulson, a neurology professor.

For the millions of families dealing with a loved one’s dementia today, hope for new treatments may seem like a dim light on the horizon that fades as their loved one moves further into their illness.

That’s why it’s also important to focus on supporting health care providers and understanding their needs through research that can impact government policy and insurance coverage—another focus of the center’s programs and research.

Research takes time, which today’s patients may not have much of. But with the help of patients and families willing to volunteer for research studies, including testing new drugs, it can be moved as soon as possible, with safeguards to make sure it’s done safely and fairly.

About this research news on Alzheimer’s disease

Author: Kara Gavin
Source: University of Michigan
Contact: Kara Gavin – University of Michigan
Image: The image is in the public domain

Original research: Open access.
“Blots on a field?” by Charles Piller. Science


Abstract

Stains on a field?

In August 2021, Matthew Schrag, a neuroscientist and physician at Vanderbilt University, received a phone call that would plunge him into a maelstrom of possible scientific misconduct. A colleague wanted to put him in touch with a lawyer who is researching an experimental drug for Alzheimer’s disease, Simufilam.

The drug’s developer, Cassava Sciences, claimed it improved cognition, in part by repairing a protein that can block sticky brain deposits of the protein amyloid beta (Aβ), a hallmark of Alzheimer’s disease.

The attorney’s clients — two prominent neuroscientists who are also short sellers and profit if the company’s stock falls — believed any research related to Simufilam may have been “fraudulent,” according to a petition later filed on their behalf with the U.S. Food and Drug Administration (FDA).

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