Is everything we think we know about Alzheimer’s wrong?

To summarize: Recent scandals in Alzheimer’s research and problems with drugs designed to help Alzheimer’s patients but failing to provide adequate results have led researchers to question the overwhelming focus on amyloid in Alzheimer’s research.

resource: University of Michigan

If you’ve followed the news about Alzheimer’s disease research over the past few months, you may have found yourself wondering where else could go wrong.

First, a highly anticipated new drug called Aduhelm was approved by the Food and Drug Administration — but its actual impact on patients was so small that most patients’ insurance would not cover it.

Then, several other promising drugs in development by drug companies were shelved or showed less impressive results in clinical trials.

Then the scandal broke: new evidence emerges science The researchers faked the images in a paper published 16 years ago — one that other researchers trusted and relied on to do their work.

How do all these developments relate to each other?

They are all related to the molecule beta-amyloid, a plaque-forming sludge that forms mucus on the outside of brain cells. Decades of research have identified this molecule as an important factor in the disease and as a potential treatment to reverse it.

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

“Amyloid does play a role in the brain and in dementia, but Alzheimer’s disease is complex, and it acts more than just one molecule,” said Dr. Henry Paulson, director of the center, who is working on his own Research lab research at Michigan Medicine and his decades of clinical care for dementia and other neurodegenerative diseases.

The paper at the center of the scandal was related to a specific form of amyloid, AB*56, thought to be an important “toxic oligomer” that promotes plaque formation.

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

“I’m more concerned about what this news will do to the public’s perception of science than our ability to make progress against this disease,” he said. The long delay in discovering so-called fakes was suboptimal, showing the importance of scientists speaking up and publishing results even if their experiments failed to prove another team’s claims. “

Such papers publishing “negative results” — papers that don’t provide good news about a potentially promising idea — are not always encouraged, as scientists have more reason to put those results aside and spend time writing about Dissertation work with potential things.

But if no one knows that efforts to reproduce scientific discoveries have failed, other scientists may turn their wheels in a dead end.

Paulson noted that it remains important to study the proteins that are cleaved or cleaved to make different forms of beta-amyloid and the consequences of the process.

But he wasn’t necessarily surprised by the failure of Aduhelm, the high-profile drug approved last year, that didn’t produce sizable effects even in the patients it tested.

The drug is not available at Michigan Medicine clinics or hospitals, and Medicare will only pay exorbitant costs for those involved in clinical trials. He added that other drugs from pharmaceutical companies that focus on beta-amyloid should be carefully scrutinized before any approval is granted.

“We think more attention needs to be paid to other factors and proteins in various dementias, from environmental factors to the immune system to specific molecules like tau, another hallmark protein of Alzheimer’s disease,” he said. explain. “In my opinion, Aduhelm’s story underscores the importance of continuing the search for additional therapeutic targets for Alzheimer’s disease and related dementias.”

Targeting amyloid, he said, could be like trying to saddle a horse that has left the barn — too much is happening in the disease process when plaque starts to form and the treatment has an impact.

Working upstream of this process and making greater use of modern tools to understand this process by studying people in the early stages of memory loss may prove to be more important.

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

Alzheimer’s and other forms of dementia are complex diseases, likely due to multiple problems in the brain over time, rather than one rogue molecule, Paulson explained. So in the end we may need to treat patients with multiple treatments at the same time, targeting several aspects of their disease — just like accepting cancer or HIV-positive patients today.

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

But at the same time, research has shown another important upstream effect that many may not be aware of, Paulson said.

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This shows the hand weight

There is abundant evidence that middle-aged and older adults who want to reduce their risk of dementia or slow the incidence of dementia should focus on healthy habits such as sleep, nutrition, exercise, social engagement, and controlling blood pressure and cholesterol.The role of lifelong education and learning – whether informal or formal – is also clear

“If you’re 70, 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 to do more to get as much sleep as possible, and to spend more time with others Build social connections,” said Paulson, professor of neurology.

For the millions of families dealing with dementia in a loved one today, the hope of new treatments seems like a glimmer of light on the horizon, fading as their loved ones slide further into the disease.

That’s why it’s also important to focus on supporting caregivers and understanding their needs through research that could impact public policy and insurance coverage — another focus of the center’s programs and research.

Research takes time, and today’s patients may not have a lot of time. But with the help of patients and families who are willing to volunteer for research, including testing of new drugs, it can act quickly, with appropriate safeguards in place to ensure it is conducted safely and honestly.

About This Alzheimer’s Research News

author: Kara Gavin
resource: University of Michigan
touch: Kara Gavin – University of Michigan
picture: Image is in the public domain

Original research: Open access.
“Stain on the Field?” Charles Peeler. science


Abstract

Spots on the field?

In August 2021, Vanderbilt University neuroscientist and physician Matthew Schrager received a call that plunged him into a spiral of possible scientific misconduct. A colleague wanted to connect him with a lawyer who was working on an experimental Alzheimer’s drug called Simufilam.

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

According to a petition later filed on their behalf with the FDA, the lawyer’s clients — two prominent neuroscientists who are also short sellers who profit if the company’s stock price falls — think some Research related to Simufilam may be “fraudulent”. Food and Drug Administration).

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