Increasing a certain protein in the brain may be able to slow the progression of Alzheimer's disease, a new study has found.
The long-held theory is that Alzheimer's disease develops when a protein called amyloid beta 42 (Aβ42) transforms into plaques that build up in the brain, damaging nerve cells and causing cognitive decline.
Researchers at the University of Cincinnati now challenge this hypothesis, suggesting that the disease is caused by low levels of healthy, functioning Aβ42, according to a university press release.
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This hypothesis is based on the fact that newly approved monoclonal antibody drugs, such as lecanemab (Leqembi) and donanemab (Kisunla), had the unintended consequence of increasing protein levels in the brain.
Increasing a certain protein in the brain may be able to slow the progression of Alzheimer's disease, a new study has found. (iStock)
“Newer Alzheimer's drugs designed to remove amyloid plaques inadvertently increase Aβ42 levels, which may explain why they have a similar or greater positive effect on cognitive function as amyloid reduction,” Alberto J. Espy, M.D., professor of neurology at the UC Parkinson's Disease and Movement Disorders Center and lead author of the study, told Fox News Digital in an email.
“Elevated Aβ42 levels after treatment were associated with slower cognitive decline, suggesting that restoring this protein to normal levels may be more beneficial for Alzheimer's patients than clearing amyloid.”
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In the study, researchers examined data from nearly 26,000 Alzheimer's disease patients who participated in 24 randomized clinical trials of a newly approved antibody treatment.
The researchers compared patients' cognitive performance before and after taking the new drug and found that increased Aβ42 was associated with “delayed cognitive impairment and clinical decline.”
The results of this study were published in the medical journal Brain on September 11th.
Understanding amyloid
Amyloid plaques aren't necessarily a bad thing, according to researchers.
“The overall evidence, along with other studies, suggests that amyloid plaques are a normally reactive brain response to a number of stressors, including infectious, toxic and biological,” Espey told Fox News Digital.
The long-held theory is that Alzheimer's disease develops when a protein called amyloid beta 42 (Aβ42) transforms into plaques that build up in the brain, damaging nerve cells and causing cognitive decline. (iStock)
“They're signs that the brain is dealing with a stressor appropriately.”
The researchers called the amyloid plaques “tombstones of Aβ42” and noted that they do not pose any harm to the brain.
“Most researchers do not believe that Alzheimer's disease is caused by just one biological mechanism.”
“Amyloid plaques do not cause Alzheimer's disease, but when the brain produces too many of them to defend itself against infections, toxins and biological changes, it is unable to produce enough Aβ42 and its levels fall below a critical threshold,” he said.
“That's when the symptoms of dementia start to appear.”
The study calls into question the long-held idea that amyloid plaques are the direct cause of Alzheimer's disease and that removing them is part of the solution.
“While beta-amyloid certainly plays an important and crucial role, we also know that tau protein, the immune system, the vascular system, metabolic health, the environment and so on all play a role in disease progression,” the Alzheimer's expert said. (AP Photo/Evan Vucci, File)
“Increasing levels of Aβ42 without clearing amyloid is entirely futile and potentially harmful, but it's worth testing as a future treatment,” Espey added.
Moving forward, the UC research team plans to investigate treatments that directly increase Aβ42 levels without targeting amyloid.
“A very complex disease”
Dr. Osama Ismail, director of scientific programs at the Alzheimer's Association in Washington, D.C., was not involved in the UC study but commented on the findings.
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“While this Aβ42-related hypothesis may prove to be part of the factors that cause or drive the progression of Alzheimer's disease, Alzheimer's is a very complex disease, and most researchers do not believe that Alzheimer's is caused by just one biological mechanism,” he told Fox News Digital.
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“Beta-amyloid certainly plays an important and critical role, but we also know that tau protein, the immune system, the vascular system, metabolic health and the environment all play a role in the disease process.”
Although FDA-approved drugs that target amyloid are currently available and in use, Ismail calls for a comprehensive approach to treating Alzheimer's disease that includes multiple approaches.
“Understanding the underlying biology and the entire mechanisms involved is crucial to expanding the pipeline of therapeutic and preventive strategies,” the experts said about Alzheimer's treatment. (iStock)
He recommends “a combination of therapeutic approaches targeting multiple mechanisms and lifestyle interventions, similar to how other major diseases such as diabetes, HIV/AIDS and heart disease are treated.”
“Understanding the underlying biology and the overall mechanisms involved is critical to expanding the pipeline of treatments and prevention strategies,” Ismail added.
Potential limitations
Espey also acknowledged the limitation that none of the published studies allowed access to individual-level data.
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“We can only work with published group-level data,” he told Fox News Digital. “Despite this limitation, the results are strongly supported.”
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Fox News Digital has reached out to Biogen, Eisai (the maker of Lukembi) and Eli Lilly (the maker of Xanla) for comment.
