Summary: Recent scandals in Alzheimer’s disease research and problems with medications designed to help people with Alzheimer’s disease but fail to produce sufficient results have left researchers questioning the large focus on amyloid beta in Alzheimer’s research.
source: University of Michigan
If you’ve been following the news regarding Alzheimer’s research in the past few months, you may find yourself wondering what else might be going on.
First, a long-awaited new drug called Aduhelm has received approval from the Food and Drug Administration — but its actual impact on patients has been so small that insurance won’t cover it for most patients.
After that, many other promising drugs in development have been sidelined by drug companies or have shown less than impressive results in clinical trials.
Then a scandal broke out: new evidence appeared Sciences Researchers falsified images in a research paper published 16 years ago – a paper that other researchers have trusted and relied on while doing their own work.
What is the relationship of all these developments to each other?
They are all bound to the molecule beta-amyloid, the plaque-forming sludge that is ejected out of brain cells. The molecule that decades of research has focused on as an important factor in disease and potential treatments to reverse it.
But in fact, scientists at the Alzheimer’s Disease Center in Michigan and elsewhere have spent years searching 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 is complex and there’s more to it than a single molecule,” says Henry Paulson, MD, who directs the center and is dedicated to Michigan Medicine’s lab research and clinical care. for dementia and other neurodegenerative diseases for decades.
The research paper at the center of the scandal concerns a specific type of amyloid, AB*56, which has been mooted as a “toxic oligomeric” that promotes plaque formation.
But Paulson says he and many of his colleagues have paid little attention to it for many years, because the researchers haven’t been able to achieve the same results that the original researchers claimed.
“I worry more about what this news might do to the public’s view of science than about our ability to make progress against this disease,” he says. The long delay in exposing the alleged falsification is not ideal, and shows the importance of scientists speaking out and publishing results even when their experiments fail to prove another team’s claim.”
This kind of publishing “negative findings” – papers that don’t provide good news about a promising idea – isn’t always encouraged because scientists have more reasons to leave these findings on the shelf and spend time writing research papers on things that are useful for the job.
But if no one knows that an attempt to reproduce a scientific discovery has failed, other scientists can spin their wheels down a dead end alley.
Paulson notes that it is still important to study the protein that is cleaved, or shredded, in order to make different forms of beta-amyloid, and the consequences of that process.
But he wasn’t necessarily surprised that Aduhelm, the much-talked-about drug that won approval last year, failed to make much of an impact even in the patients it was being tested on.
The drug is not available in Michigan Medicare clinics or hospitals, and Medicare will cover its high cost only for people participating in clinical trials. He adds that other drugs in the pipeline at drug companies that focus on beta-amyloid should be carefully screened before any approval can be obtained.
“We believe that more attention should be paid to other factors and proteins underlying different types of dementia, ranging from environmental factors, to the immune system, to specific molecules such as tau, which is another hallmark of Alzheimer’s disease,” he explains. “In my view, Aduhelm’s story underscores the importance of continuing to search for other therapeutic targets in Alzheimer’s disease and related dementia.”
Targeting amyloid for treatment might be like trying to saddle a horse that has already left the barn, he says — a lot has happened in the disease process by the time plaques start forming for treatment to make a difference.
Working in the initial stages of this process, and doing more with modern tools to understand the process by studying people in the early stages of amnesia, may be even more important.
That’s why the Alzheimer’s Disease Center in Michigan always seeks people’s participation in studies that include everything from brain scans to surveys. Anyone who wants to participate can start the process with a preliminary investigation.
Paulson explains that Alzheimer’s disease and other forms of dementia are complex diseases, likely caused by multiple errors in the brain over time, rather than a single rogue molecule. So we may end up needing to treat patients with multiple therapies simultaneously, targeting many aspects of their disease – just like cancer or HIV patients receive them today.
But in the meantime, research has already shown another important upstream effect that many people may not realize, Paulson says.
There is plenty of evidence that middle-aged and older adults who want to reduce their risk of developing dementia, or slow its onset, should focus on healthy habits such as sleep, nutrition, exercise, social participation, and controlling blood pressure and cholesterol. The role of education and lifelong learning – whether informal or formal – is also clear
“If you’re 70, I can’t tell you to go back in time and eat healthy or get in more school years, but I can tell you to make more of an effort to get as good a night’s sleep as possible,” says Paulson, professor of neuroscience.
For the millions of families dealing with the dementia of a loved one today, hope for new treatments may seem like a dim light on the horizon fading as their loved one progresses with the disease.
That’s why it’s also important to focus on supporting caregivers and understanding their needs through research that can influence public policy and insurance coverage—another focus of the center’s programs and research.
Research takes time that today’s patients may not have much. But with the help of patients and families willing to volunteer for research studies, including tests of new drugs, he can move in as quickly as possible, with safeguards in place to make sure it happens safely and honestly.
About this research on Alzheimer’s disease news
author: Kara Gavin
source: University of Michigan
Contact: Kara Gavin – University of Michigan
picture: The image is in the public domain
original search: open access.
“Stains in the field?” by Charles Beller. Sciences
Spots on the field?
In August 2021, Matthew Schrag, a neuroscientist and physician at Vanderbilt University, received a call that would plunge him into a downward spiral of potential scientific misconduct. A colleague wanted to connect him with a lawyer investigating an experimental Alzheimer’s drug called simufilam.
The drug’s developer, Cassava Sciences, claimed that it improves cognition, in part by repairing a protein that can prevent 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 who profit if the company’s stock goes down — believe some of the research on Simufilam may have been “fraudulent,” according to a petition later on their behalf to the U.S. Food and Drug Administration (FDA) .
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