Affiliations: [a]
University of Kansas Alzheimer’s Disease Research Center, Fairway, KS, USA
| [b]
Departments of Neurology, Molecular and Integrative Physiology, and Biochemistry and Molecular Biology, University of Kansas School of Medicine, Kansas City, KS, USA
Correspondence:
[*]
Correspondence to: Russell H. Swerdlow, MD, University of Kansas Alzheimer’s Disease Center, 4350 Shawnee Mission Parkway, Fairway, KS 66205, USA. Tel.: +1 913 588 0970; E-mail: rswerdlow@kumc.edu.
Abstract: 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.
