The complex pathway between amyloid β and cognition: implications for therapy

For decades, the hypothesis that brain deposition of the amyloid beta protein initiates Alzheimer's disease has dominated research and clinical trials. Targeting amyloid beta is starting to produce therapeutic benefit, although whether amyloid-lowering drugs will be widely and meaningfully effective is still unclear. Despite extensive in-vivo biomarker evidence in humans showing the importance of an amyloid cascade that drives cognitive decline, the amyloid hypothesis does not fully account for the complexity of late-life cognitive impairment. Multiple brain pathological changes, inflammation, and host factors of resilience might also be involved in contributing to the development of dementia. This variability suggests that the benefits of lowering amyloid beta might depend on how strongly an amyloid pathway is manifest in an individual in relation to other coexisting pathophysiological processes. A new approach to research and treatment, which fully considers the multiple factors that drive cognitive decline, is necessary.

Automated summary

For decades, the amyloid beta protein hypothesis has been the dominant theory in Alzheimer's disease research. While targeting amyloid beta has shown therapeutic benefits, its effectiveness is still unclear. The complexity of late-life cognitive impairment suggests that multiple factors, such as brain pathological changes and inflammation, may also contribute to dementia. Therefore, a new approach that considers all these factors is necessary for further research and treatment.