Figure 4. The mitochondrial cascade hypothesis.

The mitochondrial cascade hypothesis believes common mechanisms drive brain aging and AD pathology. The hypothesis specifically postulates mitochondrial function and cell bioenergetics constitute the shared upstream mechanism. The hypothesis states an individual’s nuclear and mitochondrial genes determine baseline mitochondrial function and durability. Mitochondrial function declines with advancing age, which influences brain aging and initiates compensatory responses. At some point these compensatory responses are no longer functionally adequate. Aβ production, tau phosphorylation, and synaptic degeneration are all downstream consequences of perturbed mitochondrial function.