Despite scientific scandal and unsuccessful drugs, scientists have made progress beyond amyloid and also shown the power of prevention.
If you have followed the news of Alzheimer’s disease research over the past few months, you might be wondering what could go wrong.
First, a long-awaited new drug called Aduhelm got Food & Drug Administration (FDA) approval — but its actual benefit for Alzheimer’s disease was so small that insurance won’t cover it for most patients.
Then, several other promising drugs in development by pharmaceutical companies were abandoned or showed less than impressive results in clinical trials.
And to top it off, a major scandal erupted. New evidence has come to light that researchers faked images in an Alzheimer’s disease study published 16 years ago. It was a high-impact paper that other researchers had trusted and relied on in their own work.
And what do all these developments of Alzheimer’s disease have to do with each other?
They are all related to the beta-amyloid molecule, the slime-forming plaque that clogs the outside of brain cells. It’s the molecule that decades of research into Alzheimer’s disease have focused on as an important contributor to the disease and key to potential treatments to reverse it.
But in fact, scientists at the Michigan Alzheimer’s Disease Center and elsewhere have spent years looking beyond amyloid in the search 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 center and has devoted his own Michigan Medicine laboratory research and clinical care to dementia and other neurodegenerative diseases for decades.
The study at the center of the scandal focuses on a specific form of amyloid, AB*56, which has been touted as an important “toxic oligomer” promoting plaque formation.
However, Paulson says he and many of his colleagues haven’t paid close attention to it for many years. This is because the researchers failed to achieve the same results as claimed by the original researchers.
“I’m more worried about the impact this news might have on the public’s perception of science than on our ability to make progress against this disease,” he says. The long delay in discovering the alleged falsehood is not ideal and shows the importance of scientists speaking up and publishing the results even when their experiments fail to prove another team’s claim.
This type of publication of “negative results” – papers that don’t provide good news about a potentially promising idea – is not always encouraged, as scientists have more reason to leave these results on the shelf and move on. time writing articles about things that make you work.
But if no one knows that an effort to replicate a scientific discovery has failed, then other scientists could get carried away.
There is ample evidence that middle-aged and older adults who want to reduce their risk of dementia or slow its onset should focus on healthy habits like sleep, exercise, nutrition, social engagement and blood pressure and cholesterol control.
Paulson notes that it is still important to study the protein that is cut, or cleaved, in order to make different forms of beta-amyloid, and the consequences of this process.
However, he is not necessarily surprised by the failure of Aduhelm, the much-talked-about drug that was approved last year, to produce any noticeable effect even in the patients it has been tested on.
The drug is not available at Michigan Medicine clinics or hospitals. Medicare will only cover its high cost for people in clinical trials. Other drugs in development at pharmaceutical companies that focus on beta-amyloid need careful consideration before getting approval, Paulson adds.
“We believe that much more attention needs to be paid to the other factors and proteins underlying various dementias, ranging from environmental factors to the immune system, to specific molecules like tau, which is the other hallmark protein of Alzheimer’s disease,” he said. “In my view, Aduhelm’s story underscores the importance of continuing to search for other therapeutic targets in Alzheimer’s disease and related dementias.”
Targeting amyloid for treatments can be like trying to saddle a horse that has already left the stable, he says – too much has happened in the disease process by the time plaques start to form for a treatment to make a big difference.
Working upstream in the process, and doing more with modern tools to understand the process by studying people in the early stages of memory loss, may prove more important.
That’s why the Michigan Alzheimer’s Disease Center is continually looking for people to participate in studies on everything from brain scans to surveys. Anyone wishing to get involved can start the process by doing an initial survey.
Alzheimer’s disease and other forms of dementia are complicated diseases and likely result from multiple problems that occur in the brain over time. It’s not just one rogue molecule, Paulson explains. So we may need to treat patients with multiple treatments at once, targeting multiple aspects of their disease – just as cancer or HIV-positive patients receive today.
But in the meantime, studies have already shown another important upstream effect that many people may not realize, Paulson says.
There is ample evidence that middle-aged and older adults who want to reduce their risk of dementia or slow its onset should focus on healthy habits like sleep, exercise, nutrition, social engagement and blood pressure and cholesterol control. 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 healthier or get more years of education, but I can tell you to do more to get a good night’s sleep as often as possible, and connect socially with other people,” says Paulson, professor of neurology.
For the millions of families struggling with the dementia of a loved one today, hope for new treatments can seem like a faint light on the horizon that fades as their loved one sinks deeper into their illness.
That’s why it’s also important to focus on supporting caregivers and understanding their needs through research that has the potential to impact public policy and insurance coverage – another goal of the programs and the center search.
Quality research takes time, which today’s patients may not have much of. However, with the help of patients and families willing to volunteer for research studies, including testing of new drugs, it can happen as quickly as possible, with safeguards in place to ensure that this happens safely and honestly.