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Why Are There No Effective Alzheimer’s Drugs?

A new study in the journal Neurology challenges the amyloid theory behind Alzheimer's disease. Maybe that's why there are no effective Alzheimer's drugs.
Why Are There No Effective Alzheimer’s Drugs?
Dementia and Alzheimer’s disease medical concept, 3D illustration. Memory loss, brain aging. Conceptual image showing blurred brain with loss of neuronal networks

According to the CDC, there are now nearly 6 million people in the U.S. with Alzheimer’s disease. Worldwide, dementia affects 50 million people. The financial, intellectual, emotional and physical toll is enormous. That’s why it is so tragic that there are no successful treatments on the horizon. Perhaps one reason we have no effective Alzheimer’s drugs is because neuroscientists have gone down the wrong path.

A Lot of Dry Holes:

For decades, scientists and drug company researchers thought the buildup of beta-amyloid brain plaque was the underlying cause of Alzheimer’s disease. This is referred to as the “amyloid-first model of Alzheimer disease (AD).”

Investigators tried all sorts of ways to combat amyloid. They were semi-successful, but nothing actually worked to slow or reverse AD. Despite billions spent on such research, the experimental compounds did not alter the inevitable downward decline.

Alzheimer’s Drugs Led to Disappointing Results:

Take the experimental drug verubecestat from Merck Sharp & Dohme. It is very good at blocking the production of beta amyloid in the brain. It should have worked.

A study published in the New England Journal of Medicine (April 11, 2019) was terminated prematurely because:

“Verubecestat did not improve clinical ratings of dementia among patients with prodromal Alzheimer’s disease, and some measures suggested that cognition and daily function were worse among patients who received verubecestat than among those who received placebo.”

One might conclude from this study that lowering amyloid plaque in the brain is probably not the answer to Alzheimer’s disease. And yet old theories die slowly. Neuroscientists and drug companies are loathe to give up on a belief that has been popular for decades. They are still developing Alzheimer’s drugs that target amyloid.

The Wrong Path?

A new study in the journal Neurology (Dec. 30, 2019)  is challenging the amyloid theory of Alzheimer’s disease.

The lead author, Kelsey Thomas, PhD, summarized the findings:

“Our research was able to detect subtle thinking and memory differences in study participants and these participants had faster amyloid accumulation on brain scans over time, suggesting that amyloid may not necessarily come first in the Alzheimer’s disease process. Much of the research exploring possible treatments for Alzheimer’s disease has focused on targeting amyloid. But based on our findings, perhaps that focus needs to shift to other possible targets.”

That summation may not help you appreciate the significance of this research. In essence, these researchers detected memory deficits and cognitive dysfunction prior to amyloid plaque buildup. Dr. Thomas suggested that:

“…amyloid may not necessarily come first in the Alzheimer’s disease process.”

An editorial in the same Neurology journal ( Dec. 30, 2019) was titled: 

“Do Subtle Cognitive Deficits Precede Amyloid Accumulation
Cart Before the Horse”

The authors note that:

“Indeed, the results of this study challenge prevailing models of both the initiating role of amyloid and the requirement of the biomarker evidence of amyloid for defining the Alzheimer continuum.”

An Alternate Theory:

We had the opportunity to interview a fascinating neuroscientist at Harvard for our syndicated public radio show. Robert D. Moir, PhD, was Assistant Professor in Neurology at Harvard Medical School. He was also Assistant Professor in Neurology at MGH Neurology Research. We were heartbroken to learn that Dr. Moir died last month at age 58 from brain cancer.

Gina Kolata wrote this in the New York Times (Dec. 20, 2019)

“Robert D. Moir, a Harvard scientist whose radical theories of the brain plaques in Alzheimer’s defied conventional views of the disease, but whose research ultimately led to important proposals for how to treat it, died on Friday at a hospice in Milton, Mass. He was 58.”

Gina Kolata describes his novel approach this way:

“Conventional wisdom held that beta amyloid accumulation was a central part of the disease, and that clearing the brain of beta amyloid would be a good thing for patients.

“Dr. Moir proposed instead that beta amyloid is there for a reason: It is the way the brain defends itself against infections. Beta amyloid, he said, forms a sticky web that can trap microbes. The problem is that sometimes the brain goes overboard producing it, and when that happens the brain is damaged.”

Learn More About Dr. Moir’s Ideas Directly:

We think Dr. Moir was onto something, especially in light of the new research published in Neurology. If you would like to hear his thoughts directly, please take a few minutes to listen to our interview with him. Here is a link to the podcast. You can hear the streaming audio by clicking on the white arrow inside the green circle under Dr. Moir’s photo. You can also download the free mp3 file or purchase a CD of the show at the bottom of the page.

Show 1132: Are Infections to Blame for Alzheimer Disease?

The idea that Alzheimer’s disease might be associated with herpes viruses is radical. It opens the door to the possibility of antivirals as Alzheimer’s drugs.

The idea that cold sores (herpes simplex virus type 1) might be associated with Alzheimer’s disease is not new. You will discover that some other investigators have been proposing this theory for decades. Here is a link to an article on this topic. In it, we pose a powerful question:

Can Anti-Herpes Treatments Prevent Alzheimer’s?

There is growing evidence to suggest that herpes viruses contribute to dementia. Could an antiviral supplement or drug like Valtrex prevent Alzheimer’s?

What Will the Future Hold for Alzheimer’s Drugs?

There is a clinical trial underway to test antivirals as Alzheimer’s drugs. It will likely take a few more years to learn whether medications such as valacyclovir (Valtrex) are helpful.

A note of cynicism: Antiviral drugs like acyclovir, valacyclovir and famciclovir have been on the market so long that they have lost their patents. The generic versions are quite affordable. Drug companies are not likely to spend hundreds of millions of dollars to test such medications against Alzheimer’s disease since they cannot make a windfall. 

We hope that the latest study about amyloid encourages neuroscientists to think more creatively. We are in desperate need of effective Alzheimer’s drugs.

Share your own thoughts about Alzheimer’s drugs in the comment section below.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.” .
  • Thomas, K. R., et al, "Objective subtle cognitive difficulties predict future amyloid accumulation and neurodegeneration," Neurology, Dec. 30, 2019, doi:10.1212/WNL.0000000000008838
  • Snitz, B. E. and Brickman, A. M., "Do subtle cognitive deficits precede amyloid accumulation? Cart before the horse," Neurology, Dec. 30, 2019, doi: 10.1212/WNL.0000000000008835
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