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P1‐197: SKELETAL MUSCLE MITOCHONDRIAL FUNCTION IN COGNITIVELY HEALTHY ELDERLY AND MCI SUBJECTS
Author(s) -
Morris Jill K.,
McCoin Colin S.,
Fuller Kelly N.Z.,
John Casey S.,
Wilkins Heather M.,
Wang Xiaowan,
Mahnken Jonathan D.,
Swerdlow Russell H.,
Thyfault John P.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.752
Subject(s) - cardiorespiratory fitness , medicine , overweight , skeletal muscle , body mass index , endocrinology , dementia , cardiology , disease
APOE4 embryonic neurons relied primarily on glucose than other fuels in terms of both dependency and capacity, whereas astrocytes could metabolize more fatty acids than neurons. APOE4 neurons and young adult astrocytes exhibited higher basal respiration but lower maximum-to-basal respiration ratio compared to APOE3 cells. Across energy fuels, APOE4 astrocytes had higher capacity metabolizing glucose than fatty acids upon high energetic demand while such a fuel preference was much less significant in APOE3 astrocytes. Consistently, the maximal capacity in metabolizing fatty acids was significantly lower in APOE4 astrocytes when compared to APOE3 astrocytes. Conclusions: Our findings indicated that the impact of APOE genotype on brain bioenergetics is cell type, AD, and stage-dependent. It was suggested that the development of strategies to restore brain energy metabolism against AD should consider APOE genotype, age and disease-stage, and the fuel preference of different cell types in the brain. This work was supported by NIA P01AG026572 to RDB (Project 1 to RDB & FY, Analytic Core to FY), University of Arizona Center for Innovation in Brain Science startup fund to FY, and Arizona Alzheimer’s Consortium Pilot Project grants to RDB and to FY.