2024
mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer’s disease in an APOE genotype-dependent manner
Sanganahalli B, Mihailovic J, Vekaria H, Coman D, Yackzan A, Flemister A, Aware C, Wenger K, Hubbard W, Sullivan P, Hyder F, Lin A. mTOR inhibition enhances synaptic and mitochondrial function in Alzheimer’s disease in an APOE genotype-dependent manner. Cerebrovascular And Brain Metabolism Reviews 2024, 44: 1745-1758. PMID: 38879800, PMCID: PMC11494852, DOI: 10.1177/0271678x241261942.Peer-Reviewed Original ResearchResponse to rapamycinE3FAD miceMitochondrial functionAlzheimer's diseaseMammalian target of rapamycinAD genetic risk factorsApolipoprotein E4Neuronal mitochondrial functionMitochondrial oxidative metabolismE4FAD miceHuman APOE4 geneTCA cycle rateGenetic risk factorsGenotype-dependent mannerE3FADTarget of rapamycinAPOE4 geneAPOE3 alleleGlutamate-glutamine cycleAPOE4 carriersBioenergetic measurementsE4FADMetabolic functionsAPOE genotypeMammalian target of rapamycin inhibition
2020
APOE genotype-dependent pharmacogenetic responses to rapamycin for preventing Alzheimer's disease
Lin AL, Parikh I, Yanckello LM, White RS, Hartz AMS, Taylor CE, McCulloch SD, Thalman SW, Xia M, McCarty K, Ubele M, Head E, Hyder F, Sanganahalli BG. APOE genotype-dependent pharmacogenetic responses to rapamycin for preventing Alzheimer's disease. Neurobiology Of Disease 2020, 139: 104834. PMID: 32173556, PMCID: PMC7486698, DOI: 10.1016/j.nbd.2020.104834.Peer-Reviewed Original ResearchConceptsCerebral blood flowAsymptomatic APOE4 carriersE4FAD miceAPOE4 carriersAlzheimer's diseaseCerebrovascular reactivityNeurotransmitter levelsE3FAD micePharmacogenetic responsePharmacogenetic differencesSomatosensory responsesBlood-brain barrier functionBrain functionStrongest genetic risk factorBrain metabolic changesFree fatty acid levelsAmyloid-beta plaquesHuman APOE4 geneDifferent APOE allelesAPOE ε3 alleleFuture clinical testingGenetic risk factorsFatty acid levelsWhite matter integrityAβ transport