ArticleNeurobiology of disease2025
APOE4 reshapes the lipid droplet proteome and modulates microglial inflammatory responses.
Article in Neurobiology of disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed.
- Hippocampal AdipoR1 regulates the microglial response and delays disease progression in a mouse model of Alzheimer's disease.Molecular psychiatry · 2026Article
- Older adult APOE4 mice exhibit modest immunometabolic adaptation following microglial APOE2 replacement.Neurobiology of aging · 2026Article
- APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics.Nature communications · 2026Article
- Article
- Reshaping the immune landscape: next-generation microglia-targeted therapies for Alzheimer's disease.Biological research · 2026Review
- ApoE lipoproteins in the central nervous system under homeostasis and role in Alzheimer's disease and related disorders.Molecular neurodegeneration · 2026Review
- APOE4 negates the effects of ovarian hormones on cerebrovascular endothelial and mitochondrial function.The Journal of physiology · 2026Article
- PYGL-driven glycogenolysis impairs microglial autophagic fluxActa pharmaceutica Sinica. B · 2026Article
- Alzheimer's Disease as a Disorder of Neuroimmune Dysregulation.Neurology international · 2026Review
- Apolipoprotein E4 in Alzheimer's Disease: Role in Pathology, Lipid Metabolism, and Drug Treatment.International journal of molecular sciences · 2026Review
- Nutritional substrates and microglial metabolic fitness in brain aging and Alzheimer's disease: from lipid handling to TREM2-linked translation.Frontiers in nutrition · 2026Review
- Cholinergic regulation of neuroinflammation: linking microglia, immunometabolism, and neuromodulation.Frontiers in immunology · 2026Review
- APOE-Glia Crosstalk in Epilepsy: Mechanisms, Controversies, and Therapeutic Perspectives.Journal of inflammation research · 2026Review
- Role of apolipoprotein E4 in alzheimer's disease pathogenesis and emerging therapeutic strategies.Metabolic brain disease · 2025Review
- Neuronal APOE4 drives damaging lipid accumulation via contact-dependent neuron-oligodendrocyte-microglia interaction in Alzheimer's disease.bioRxiv : the preprint server for biology · 2025Article
- Article
- APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- Neurobiological Correlates of Coping Strategies in PTSD: The Role of IGF-1, CASP-9, nNOS, and IL-10 Based on Brief-COPE Assessment.Current issues in molecular biology · 2025Article
- Lipid and lipoprotein metabolism in microglia: Alzheimer's disease mechanisms and interventions.Journal of lipid research · 2025Review
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Abstract
Excess lipid droplet (LD) accumulation is implicated in various diseases, including Alzheimer's disease (AD), yet the mechanisms underlying this accumulation remain unclear. Apolipoprotein E (ApoE) is a droplet-associated protein, and its E4 variant confers the greatest genetic risk for late-onset AD while also being linked to increased neuroinflammation and LD accumulation. In this study, we compared the lipid and protein composition of hepatic LDs in targeted replacement mice expressing human E3 (neutral) or E4 (risk variant), under both baseline conditions and following lipopolysaccharide (LPS) administration. Lipidomic analysis revealed that E4 LDs exhibit a shift in glycerophospholipid distribution, with an increase in phosphatidylcholine species, such that their baseline profile resembles that of LPS-treated LDs. Quantitative proteomics indicated that E4 LDs are enriched in proteins related to vesicle transport but show decreased levels of proteins involved in fatty acid β-oxidation. Notably, many LD-associated proteins overlapped with those identified in AD postmortem and microglial 'omics studies, suggesting a role for LDs in AD pathogenesis. To further explore these findings, primary microglia from E3 and E4 mice were exposed to exogenous lipids, LPS, and necroptotic N2A cells. Under most conditions, E4 microglia accumulated more LDs and secreted higher levels of proinflammatory cytokines (TNF, IL-1β, IL-10) compared to E3 microglia, although their LPS response was blunted. These data suggest that altered LD dynamics in E4 microglia may contribute to the increased AD risk associated with APOE4.
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