Alzheimer’s Controversy: Have Scientists Gotten It All Wrong?

Scientists are believed to have made giant strides in research, expanding the frontiers of knowledge on Alzheimer’s disease. However, recent events – perhaps, most notably a bogus study scandal – are casting doubt on what is already known.

Alzheimer’s disease

An investigative report revealed in recent weeks that a study, which many scientists have relied on for their work, was altered to deceive. Evidence suggested that images used in the study to back a popular theory of how Alzheimer’s develops were fake.

There is also the case of unimpressive effects of a highly-anticipated medication that was approved for patients by the U.S. Drug and Food Administration (FDA). Add to that the mediocre results from clinical trials testing drugs that were thought promising and you may start to wonder if scientists got it wrong all this time.

However, Henry Paulson and some other researchers at the University of Michigan are not part of those that have focused attention on the molecule that was identified as the main cause of Alzheimer’s in the controversial study.

A complicated disease

Like other types of dementia, Alzheimer’s is a very difficult disease to understand. Paulson argues that just one factor cannot be blamed for its occurrence; multiple factors are likely involved.

The study that stirred the recent controversy identified a form of amyloid called AB*56 as a central factor in the incidence of this disorder. It identified the molecule as a key “toxic oligomer” that supports the formation of plaques seen in Alzheimer’s.

Therefore, beta-amyloid has been a focus of research into this disease for many years. Efforts to develop treatments have often revolved around it.

Paulson says he and his fellow scientists at the Michigan Alzheimer’s Disease Center haven’t paid much attention to the paper. They have refused to limit themselves to just focusing on beta-amyloid. This is especially because other researchers have found it hard to replicate the results from the now-contentious study.

“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,” says Paulson, who is the director of the Michigan Alzheimer’s Disease Center.

He expresses worry about what the study scandal could do to how science is viewed by the people. Hiding “negative results” also has the tendency of leading other researchers down the wrong road.

Paulson has spent years trying to find out the root causes of Alzheimer’s, without limiting his focus to only amyloid. His research and clinical care at Michigan Medicine are dedicated to dementia and other neurodegenerative disorders.

The professor of neurology was, therefore, not surprised about the failure of Aduhelm that was approved last year for the treatment of patients. He revealed that the drug, which targets amyloid, is currently not available at Michigan Medicine hospitals or clinics.

Way forward

Paulson compares using treatments to target only amyloid with saddling a horse that has bolted from the barn. A lot of damage would have already been done by the time plaques start to form, he said. It is vital to unravel what occurs early on in the occurrence of the disease.

“We believe much more attention needs to be paid to 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,” argues Paulson. “In my view, the Aduhelm story underscores the importance of continuing to look for other therapeutic targets in Alzheimer’s disease and related dementia.”

He wants greater scrutiny of other drugs targeting beta-amyloid that pharmaceutical companies are currently working on before being granted approval.

It is critical to look more into the proteins that are cut up to make various beta-amyloid forms, Paulson states. The outcomes of that process need to be probed.

There is a need for patients and their families to be more open to volunteering for clinical research. This can help to make the process of finding effective treatments faster. The Michigan Alzheimer’s Disease Center is constantly looking for people to volunteer for different studies.

On the bright side, science has revealed a lot about what can be done to reduce the risk of dementia. There is ample evidence that good nutrition, exercise, quality sleep, cholesterol control, and other healthy habits can help. Social engagement and lifelong learning could also be valuable.