Is everything you know about Alzheimer's wrong?

Aug. 2, 2022
Despite a scientific scandal and unsuccessful drugs, researchers have made strides beyond amyloid, and shown the power of prevention too.

If you’ve followed the news about Alzheimer’s disease research in the past few months, you might find yourself wondering what else could go wrong.

First, a much-anticipated new drug called Aduhelm got approval from the Food & Drug Administration – but its actual effect on patients was so small that insurance won’t cover it for most patients.

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

And then a scandal broke: New evidence came to light that researchers had faked images in a paper published 16 years ago – a paper that other researchers had trusted and relied on as they did their own work.

What do all of these developments have to do with one another?

They’re all tied to the molecule beta-amyloid, the plaque-forming sludge that gunks up the outside of brain cells. The molecule that decades of research has focused on as an important factor in the disease and potential 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 there’s much more to it than one molecule,” said Henry Paulson, M.D., Ph.D., who directs the center and has devoted his own laboratory’s research at Michigan Medicine and his clinical care to dementia and other neurodegenerative diseases for decades.

The paper at the center of the scandal has to do with a specific form of amyloid, AB*56, that was put forth as an important “toxic oligomer” encouraging plaque formation.

This kind of publishing of “negative results” – papers that don’t 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 papers about things that do work.

But if no one knows that an effort to reproduce a scientific discovery has failed, then other scientists could spin their wheels driving down a blind alley.

The drug is not available at the clinics or hospitals of Michigan Medicine, and Medicare will only cover its high cost for people taking part in clinical trials. Other drugs in the pipeline at drug companies that focus on beta-amyloid should be scrutinized carefully before getting any approval, he adds.

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

U of M Health release