ApoE4 Impairs Neuron-Astrocyte Coupling of Fatty Acid Metabolism.

ABSTRACT: Alzheimer's disease (AD) risk gene ApoE4 perturbs brain lipid homeostasis and energy transduction. However, the cell-type-specific mechanism of ApoE4 in modulating brain lipid metabolism is unclear. Here, we describe a detrimental role of ApoE4 in regulating fatty acid (FA) metabolism across neuron and astrocyte in tandem with their distinctive mitochondrial phenotypes. ApoE4 disrupts neuronal function by decreasing FA sequestering in lipid droplets (LDs). FAs in neuronal LDs are exported and internalized by astrocytes, with ApoE4 diminishing the transport efficiency. Further, ApoE4 lowers FA oxidation and leads to lipid accumulation in both astrocyte and the hippocampus. Importantly, diminished capacity of ApoE4 astrocytes in eliminating neuronal lipids and degrading FAs accounts for thei

SUBMITTER: Qi G 

PROVIDER: S-EPMC7837265 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature