Scientists Challenge Core Alzheimer's Theory: Protein Loss, Not Plaques, May Drive Disease
A groundbreaking study by University of Cincinnati researchers challenges the traditional amyloid cascade hypothesis in Alzheimer's disease, suggesting that restoring Aβ42 protein levels, rather than removing plaques, may be more effective for treatment.
New research from the University of Cincinnati has challenged decades of thinking about Alzheimer's disease treatment. The study, published in Brain, suggests that the loss of a specific protein might be more important for disease progression than the buildup of brain plaques that scientists have long targeted.
The research team, led by Professor Alberto J. Espay, analyzed data from 24 clinical trials involving nearly 26,000 patients. They found that increasing levels of the amyloid-beta 42 (Aβ42) protein in cerebrospinal fluid showed similar positive effects on cognitive function as removing amyloid plaques – the traditional target of Alzheimer's treatments.
This finding contradicts the dominant "amyloid cascade hypothesis" that has guided Alzheimer's research since the 1990s. That theory suggested that clumping of Aβ42 into plaques caused the disease's devastating cognitive decline. However, multiple clinical trials targeting plaque removal have failed to show significant benefits.
The study revealed that newer monoclonal antibody treatments (aducanumab, lecanemab, and donanemab) might work not just by clearing plaques but by increasing Aβ42 levels. This dual action could explain why these treatments show more promise than earlier approaches focused solely on plaque removal.
"We have thought that the only explanation for any potential benefit of the newly approved monoclonal antibodies for Alzheimer's is that they are good at removing amyloid plaques from the brain," Espay explained. "Yet many other interventions have done that in the past, to no avail."
The research suggests that Aβ42 plays a vital role in maintaining brain health, and its depletion – not its accumulation into plaques – might be the real problem. This perspective shift could lead to new treatment approaches focusing on restoring normal protein levels rather than eliminating plaques.
While promising, the study has limitations. The researchers worked with aggregated trial data rather than individual patient information, potentially missing important nuances. Additionally, current treatments that increase Aβ42 levels can cause side effects like brain inflammation and shrinkage.
These findings open new avenues for Alzheimer's research and treatment development. Future studies might focus on safely increasing Aβ42 levels without the complications of current antibody treatments.
Read the full study: [URL: https://www.psypost.org/neuroscientists-just-turned-a-major-alzheimers-theory-on-its-head/]
