Format

Send to

Choose Destination
Front Aging Neurosci. 2016 Oct 4;8:232. eCollection 2016.

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

Author information

1
Department of Clinical Pharmacy, School of Pharmacy, University of Southern California Los Angeles, CA, USA.
2
Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California Los Angeles, CA, USA.

Abstract

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.

KEYWORDS:

APOE; Alzheimer’s disease; haplogroup; mitochondria; sex

Supplemental Content

Full text links

Icon for Frontiers Media SA Icon for PubMed Central
Loading ...
Support Center