Could vaccines prevent and treat Alzheimer’s disease?

Scientists are testing vaccines as potential treatments for Alzheimer’s, in an attempt to reign in harmful immune activity tied to the disease.

Beta-amyloid (orange) accumulates in the brains of people with Alzheimer’s disease.  (Image credit: selvanegra via Getty Images)

Despite decades of Alzheimer’s research, scientists have not found a treatment that halts or dramatically slows the disease.

Scientists are investigating if a completely new approach – so-called Alzheimer’s vaccines – could alter the disease’s course.

What is the logic behind this effort? Much of the previous research has placed beta-amyloid plaques, clumps of protein that accumulate in the brains of Alzheimer’s patients, front and center.

So some researchers have proposed that the plaques are a consequence, rather than a cause of Alzheimer’s.

This idea is bolstered by evidence that people infected with certain viruses, including the herpes virus and potentially SARS-CoV-2, face a heightened risk of later Alzheimer’s disease.

Now, researchers are testing vaccines as potential Alzheimer’s treatments, in an attempt to retrain the immune system to fight the disease.

These vaccines would theoretically work by stimulating the cells that clear beta-amyloid while shutting down the immune cascade responsible for releasing the harmful protein.

The shots could both be used to help prevent Alzheimer’s and to treat the disease, once it’s developed.

One potential Alzheimer’s vaccine has existed for a century.

In two observational studies comprising thousands of patients, scientists noted that bladder cancer patients inoculated with the BCG vaccine have lower odds of developing Alzheimer’s in the next several years.

That raised the possibility that the vaccine helps prevent Alzheimer’s, at least in the five years after inoculation.

One theory for why BCG might stave off Alzheimer’s is that it retrains the immune system.

Now, BCG is being tested in a small clinical trial of 15 adults with mild cognitive impairment and mild-to-moderate Alzheimer’s, to see how it affects measurable signs of the conditions.

BCG isn’t the only immune-modulating shot being tested in Alzheimer’s.

Dr. Tanuja Chitnis, a professor of neurology at Harvard Medical School and at Brigham and Women’s Hospital, is leading the development of a nasal Alzheimer’s vaccine.

A 2008 mouse study suggests Protollin doesn’t directly train the immune system to attack beta-amyloid but rather broadly activates immune cells so that they eat the proteins.

In theory, Protollin could also make the immune cells more responsive to the bacteria and viruses thought to raise the risk of Alzheimer’s in the first place.

Current Alzheimer’s drugs, like aducanumab and lecanemab, deliver antibodies that specifically stick to and help clear amyloid plaques in the brain.

Several companies are developing Alzheimer’s vaccines that directly target beta-amyloid.

One side effect to look out for is autoimmunity, James Nowick, a professor of chemistry at the University of California, Irvine who co-authored a review about the potential of Alzheimer’s vaccines, told Live Science.

“A vaccine could thus produce a serious autoimmune response.” It isn’t as simple as turning inflammation on or off – in Alzheimer’s, the microglia aren’t active while other processes that release beta-amyloid might be hyperactive.

In contrast to the approved antibodies BCG and Protollin have a track-record of safety, as they’re already approved for other conditions or as ingredients in other vaccines.

Beyond their safety, the effectiveness of these Alzheimer’s vaccines also remains to be proven.

Even if vaccines work no better than existing monoclonal antibodies they could make Alzheimer’s treatment more accessible.

“In more established diseases, ongoing treatment may be required.” And if the vaccines leave a lasting mark on immune cells, as seen in some studies of BCG, perhaps that could mean fewer doses or treatments will be required in the long run.

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