Everything you think you know about Alzheimer’s is wrong?

Summary: Recent scandals in Alzheimer’s research and problems with drugs designed to help Alzheimer’s patients that fail to produce sufficient results have researchers questioning the overwhelming focus on amyloid-beta in Alzheimer’s research.

A source: University of Michigan

If you’ve been following the news about Alzheimer’s research over the past few months, you might be wondering what else could go wrong.

First, a long-awaited new drug called Aduhelm received approval from the Food and Drug Administration, but its effects on patients are so small that insurance won’t cover it for most patients.

Subsequently, several other promising drugs developed by pharmaceutical companies were rejected or showed less impressive results in clinical trials.

And then there was a scandal: new evidence appeared science researchers created fake images in a paper published 16 years ago—a paper that other researchers trusted and relied on when doing their work.

And how do all these stories relate to each other?

All of them are bound to the beta-amyloid molecule, a plaque-forming sludge that breaks down the outside of brain cells. Decades of research have focused on this important factor in disease and potential treatments to reverse it.

But in fact, scientists at the Michigan Alzheimer’s Disease Center and elsewhere have looked beyond amyloid for years to find 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 in dementia, but Alzheimer’s disease is complex and there’s more to it than just one molecule,” said Henry Paulson, MD, Ph.D., who directs the center and dedicates his personal work to it. Laboratory research at Michigan Medicine and its clinical care for dementia and other neurodegenerative diseases span decades.

The paper at the center of the scandal concerns a particular form of amyloid, AB*56, which has been touted as an important “toxic oligomer” that triggers plaque formation.

But Paulson says he and his colleagues didn’t pay much attention to it over the years because researchers couldn’t reach the conclusions the original researchers had suggested.

“I’m more concerned about how this news might affect the public’s view of science than our ability to make progress against this disease,” he says. The length of time it takes to uncover fake facts is far from ideal, and highlights the importance of scientists speaking up and publishing results even when their experiments fail to prove the other team’s claim.

Publishing “negative results” that do not bode well for a potentially promising idea is not always encouraged, as scientists have more reason to shelve those results and waste time. the work.

But if no one knows that an attempt to recreate a scientific discovery has failed, other scientists may end up driving their wheels down a blind alley.

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

But he is not surprised that the much-discussed drug Adukhelm, which was approved last year, has failed to produce a significant effect in patients tested.

The drug is not available at Michigan Medicine clinics or hospitals, and Medicare only covers its high cost for people participating in clinical trials. Other drugs in the pipeline from drug companies targeting beta-amyloid will need to be thoroughly tested before any approval, he adds.

“We believe that more attention should be paid to other factors and proteins that underlie various dementias, from environmental factors to the immune system to certain molecules such as tau, another hallmark of Alzheimer’s disease,” he explains. “I think the Aduhelm case highlights the importance of continuing to search for other therapeutic targets for Alzheimer’s disease and related dementias.”

Targeting amyloid for treatment can be like trying to saddle a horse that’s broken out of the barn, he says — when too much happens in the disease process and plaques start to form to treat, the change happens.

It may be more important to work upstream of the process and do more with modern tools to understand the process by studying people in the early stages of memory loss.

That’s why the Michigan Alzheimer’s Center is always looking to get people involved in research, from brain scans to surveys. Anyone interested in participating can begin the process by completing an initial survey.

Alzheimer’s and other forms of dementia are complex diseases and can be caused by many things going wrong in the brain over time, rather than just one faulty molecule, Paulson explains. Thus, we may need to treat patients with several treatments at the same time, several aspects of their disease – like cancer or HIV-positive patients.

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

But in the meantime, another important study showed an effect that many people don’t understand, Paulson says.

See also

This indicates the weight of the arm

There is a growing body of evidence that middle-aged and older adults who want to reduce their risk of dementia or delay its onset should focus on good health, such as sleep, diet, exercise, social activity, and controlling blood pressure and cholesterol. The role of lifelong education and training — whether formal or informal — is also clear

“If you’re 70 years old, I can’t tell you to go back in time and eat healthier or get years of schooling, but I can tell you to go to bed as often as possible and do more to get a good night’s sleep. in social contact with other people,” says Paulson, professor of neurology.

For the millions of families today dealing with dementia in a loved one, the hope of a new treatment can seem like a dim light that fades each time their loved one falls ill.

Therefore, it is also important that another focus of the Center’s programs and research focus on supporting caregivers and understanding their needs through research that can influence public policy and insurance.

Research takes time, and current patients may not have much time. But with the help of patients and families willing to volunteer for research, including new drug trials, it can move as quickly as possible and safeguards can be put in place to make it safe and honest.

This is Alzheimer’s research news

Author: Look Gavin
A source: University of Michigan
The connection: Kara Gavin – University of Michigan
Photo: Image is in the public domain

Original research: Open access.
“Spots in the field?” By Charles Peeler. science


Abstract

Spots in the field?

In August 2021, Vanderbilt University neuroscientist and physician Matthew Schrag received a phone call that plunged him into a whirlwind of possible scientific misconduct. A wanted colleague put him in touch with an attorney who was researching an experimental Alzheimer’s drug called Simufilam.

Cassava Sciences, the drug’s developer, claims it improves cognition in part by modifying a protein that blocks the sticky brain deposits of the amyloid beta (Aβ) protein that is a hallmark of Alzheimer’s.

The lawyer’s clients — two prominent neuroscientists who are short sellers who stand to profit if the company’s stock falls — believed that some research involving Simufilam might be “fraudulent,” according to a petition later filed on their behalf with the U.S. Food and Drug Administration (FDA ).

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