The Alzheimer's Disease Mitochondrial Cascade Hypothesis: A Current Overview

Viable Alzheimer's disease (AD) hypotheses must account for its age-dependence; commonality; association with amyloid precursor protein, tau, and apolipoprotein E biology; connection with vascular, inflammation, and insulin signaling changes; and systemic features. Mitochondria and parameters influenced by mitochondria could link these diverse characteristics. Mitochondrial biology can initiate changes in pathways tied to AD and mediate the dysfunction that produces the clinical phenotype. For these reasons, conceptualizing a mitochondrial cascade hypothesis is a straightforward process and data accumulating over decades argue the validity of its principles. Alternative AD hypotheses may yet account for its mitochondria-related phenomena, but absent this happening a primary mitochondrial cascade hypothesis will continue to evolve and attract interest.

Automated summary

Viable hypotheses about Alzheimer's disease must consider its age-dependence, commonality, association with specific biological factors, connection with various changes in the body, and systemic features. Mitochondria and factors influenced by mitochondria may link these different characteristics. The mitochondrial cascade hypothesis provides a straightforward explanation and accumulating data support its validity. While alternative hypotheses may also explain mitochondria-related phenomena, the primary mitochondrial cascade hypothesis will continue to evolve and attract interest.