Triad of Risk for Late Onset Alzheimer's: Mitochondrial Haplotype, APOE Genotype and Chromosomal Sex.

TitleTriad of Risk for Late Onset Alzheimer's: Mitochondrial Haplotype, APOE Genotype and Chromosomal Sex.
Publication TypeJournal Article
Year of Publication2016
AuthorsWang Y, Brinton RD
JournalFront Aging Neurosci
Date Published2016

Brain is the most energetically demanding organ of the body, and is thus vulnerable to even modest decline in ATP generation. Multiple neurodegenerative diseases are associated with decline in mitochondrial function, e.g., Alzheimer's, Parkinson's, multiple sclerosis and multiple neuropathies. Genetic variances in the mitochondrial genome can modify bioenergetic and respiratory phenotypes, at both the cellular and system biology levels. Mitochondrial haplotype can be a key driver of mitochondrial efficiency. Herein, we focus on the association between mitochondrial haplotype and risk of late onset Alzheimer's disease (LOAD). Evidence for the association of mitochondrial genetic variances/haplotypes and the risk of developing LOAD are explored and discussed. Further, we provide a conceptual framework that suggests an interaction between mitochondrial haplotypes and two demonstrated risk factors for Alzheimer's disease (AD), apolipoprotein E (APOE) genotype and chromosomal sex. We posit herein that mitochondrial haplotype, and hence respiratory capacity, plays a key role in determining risk of LOAD and other age-associated neurodegenerative diseases. Further, therapeutic design and targeting that involve mitochondrial haplotype would advance precision medicine for AD and other age related neurodegenerative diseases.

Alternate JournalFront Aging Neurosci
PubMed ID27757081
PubMed Central IDPMC5047907
Grant ListP01 AG026572 / AG / NIA NIH HHS / United States
R01 AG032236 / AG / NIA NIH HHS / United States
Faculty Member Reference: 
Roberta Diaz Brinton, Ph.D