A recent study published in Brain challenges long-held assumptions about Alzheimer’s disease treatment. Researchers at the University of Cincinnati found that new monoclonal antibody drugs may slow cognitive decline by increasing levels of a critical brain protein called amyloid-beta 42 (Aβ42), rather than simply reducing amyloid plaques in the brain.
Alzheimer’s disease is the most common form of dementia, characterized by progressive memory loss, cognitive decline, and changes in behavior. The condition gradually impairs daily functioning and quality of life, affecting millions of people worldwide.
The study analyzed data from 24 randomized clinical trials of monoclonal antibody drugs designed to target amyloid plaques. These trials included nearly 26,000 patients diagnosed with early or moderate Alzheimer’s disease. The researchers focused on changes in two key biomarkers: amyloid plaque levels and cerebrospinal fluid levels of Aβ42.
The results showed that increases in Aβ42 levels were just as strongly associated with cognitive improvement as the reduction of amyloid plaques. In fact, drugs that raised Aβ42 levels showed a consistent correlation with better cognitive outcomes. Conversely, treatments that lowered Aβ42 levels worsened cognitive performance.
The researchers proposed that amyloid plaques might not directly cause Alzheimer’s symptoms. Instead, plaques could represent a protective response by the brain to stress or injury. The real issue, they suggested, might be the depletion of soluble Aβ42, which plays a critical role in neuron health and synaptic function.
However, the study has limitations. The researchers relied on aggregated data from clinical trials, which may limit the precision of their analyses. Looking forward, the team hopes to test the potential benefits of directly increasing Aβ42 without the toxicities imposed upon the brain by removing amyloid.
The findings highlight that there are two sides to any story. Alzheimer’s treatment has been focused on reducing amyloid plaques, but many other interventions have done so in the past with limited success. The alternative explanation for potential benefit is the increase in Aβ42 levels, which most antibodies accomplish.
The study, led by Alberto J. Espay, provides new insights into the complex relationship between amyloid-beta 42 and Alzheimer’s disease progression. While the results are promising, further research is needed to fully understand the mechanisms at play and to develop more effective treatments for this devastating disease.
Source: https://www.psypost.org/neuroscientists-just-turned-a-major-alzheimers-theory-on-its-head