[Source – hopkinsmedicine]
Link Between Protein Levels and Cognitive Benefits
A new study published in the journal Brain reveals that increases in certain brain protein levels may slow cognitive impairment in Alzheimer’s disease patients as effectively as the reduction of amyloid plaques, traditionally considered the primary therapeutic target. Conducted by researchers at the University of Cincinnati (UC), the study challenges the widely held belief that the newly approved monoclonal antibodies primarily benefit patients by clearing amyloid plaques from the brain. The research team, led by Dr. Alberto Espay, found that the unintended rise in levels of a crucial brain protein, amyloid-beta 42 (Aβ42), correlates equally well with cognitive improvements.
Understanding the Study and Its Findings
For years, the prevailing theory has been that Alzheimer’s disease is driven by the accumulation of amyloid plaques, formed when amyloid-beta 42 (Aβ42) hardens into clumps. However, Dr. Espay and his colleagues propose that the decline in soluble Aβ42, rather than the build-up of plaques, is the root cause of the disease in Alzheimer’s disease patients. According to their research, dementia occurs not when plaque levels are high, but when Aβ42 levels fall significantly low. The team observed that new monoclonal antibody drugs, which were approved for their ability to reduce amyloid plaques, also increased Aβ42 levels in Alzheimer’s disease patients’ brains.
The study involved an analysis of data from 26,000 patients across 24 randomized clinical trials using these new antibody treatments. The researchers assessed cognitive impairment and changes in Aβ42 levels before and after the treatments. They discovered that patients with higher Aβ42 levels post-treatment experienced slower cognitive decline, suggesting that increased levels of Aβ42 might be just as predictive of cognitive benefits as the reduction of amyloid plaques.
Implications for Alzheimer’s Treatment Strategies
These findings present a new perspective on the mechanisms underlying cognitive improvement in Alzheimer’s disease patients. Dr. Espay argues that since increasing Aβ42 levels appears to enhance cognition, the focus should shift towards therapies that directly raise Aβ42 levels, rather than solely targeting amyloid reduction. “If the problem with Alzheimer’s is the loss of the normal protein, then increasing it should be beneficial,” he explained.
However, Espay also highlighted a significant dilemma for clinicians. While monoclonal antibody treatments might inadvertently boost Aβ42 levels, they also reduce amyloid plaques, which can be toxic and lead to accelerated brain shrinkage. He emphasized that therapies need to increase Aβ42 without the potentially harmful effects of amyloid reduction.
Going forward, Dr. Espay and his team are focusing their research on developing treatments that directly elevate Aβ42 levels, offering a potential alternative therapeutic approach to address the complexities of Alzheimer’s disease patients.
