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The cell biology of APOE in the brain.
- Source :
-
Trends in cell biology [Trends Cell Biol] 2024 Apr; Vol. 34 (4), pp. 338-348. Date of Electronic Publication: 2023 Oct 05. - Publication Year :
- 2024
-
Abstract
- Apolipoprotein E (APOE) traffics lipids in the central nervous system. The E4 variant of APOE is a major genetic risk factor for Alzheimer's disease (AD) and a multitude of other neurodegenerative diseases, yet the molecular mechanisms by which APOE4 drives disease are still unclear. A growing collection of studies in iPSC models, knock-in mice, and human postmortem brain tissue have demonstrated that APOE4 expression in astrocytes and microglia is associated with the accumulation of cytoplasmic lipid droplets, defects in endolysosomal trafficking, impaired mitochondrial metabolism, upregulation of innate immune pathways, and a transition into a reactive state. In this review, we collate these developments and suggest testable mechanistic hypotheses that could explain common APOE4 phenotypes.<br />Competing Interests: Declaration of interests The authors declare no competing interests.<br /> (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Humans
Mice
Alzheimer Disease genetics
Alzheimer Disease metabolism
Astrocytes metabolism
Neurodegenerative Diseases genetics
Neurodegenerative Diseases metabolism
Apolipoprotein E4 genetics
Apolipoprotein E4 metabolism
Apolipoproteins E genetics
Apolipoproteins E metabolism
Brain metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3088
- Volume :
- 34
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Trends in cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 37805344
- Full Text :
- https://doi.org/10.1016/j.tcb.2023.09.004