Triad of risk for late onset Alzheimer's: Mitochondrial haplotype, apoe genotype and chromosomal sex

Yiwei Wang, Roberta D. Brinton

Research output: Contribution to journalReview articlepeer-review

39 Scopus citations


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.

Original languageEnglish (US)
Article number232
JournalFrontiers in Aging Neuroscience
Issue numberOCT
StatePublished - Oct 4 2016
Externally publishedYes


  • APOE
  • Alzheimer's disease
  • Haplogroup
  • Mitochondria
  • Sex

ASJC Scopus subject areas

  • Aging
  • Cognitive Neuroscience


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