Brain aging, Alzheimer's disease, and mitochondria

The relationship between brain aging and Alzheimer's disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself.

► Whether Alzheimer's disease and brain aging are mechanistically linked is contentious.
► New definitions of Alzheimer's disease infer most very elderly individuals have some form of it.
► Beta amyloid homeostasis is regulated by bioenergetic stress.
► Mitochondria may constitute a mechanistic link between Alzheimer's disease and brain aging.