ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2025
APOE4 impairs autophagy and Aβ clearance by microglial cells.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.Journal of neurology · 2025Pooled it
- ApoE lipidation state directs immunometabolic reprogramming of human microglia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Small-Molecule NANT Therapeutics Targeting the Brain-Immune Axis in Alzheimer's Disease: Mechanisms, Clinical Progress, and Translational Challenges.Molecules (Basel, Switzerland) · 2026Review
- APOE genotypes differentially remodel the astrocytic lipid droplet proteome to shape lipid droplet dynamics.Nature communications · 2026Article
- Digital quantification of vascular β-amyloid and perivascular plaques in cerebral amyloid angiopathy.Research square · 2026Article
- APOE4 disrupts the central dogma by arresting neuronal proteome dynamics.bioRxiv : the preprint server for biology · 2026Article
- Microglial mitophagy as an immunometabolic checkpoint in alzheimer's disease: linking mitochondrial quality control to neuroinflammation.Journal of neuroinflammation · 2026Review
- Alzheimer's Disease Risk AllelebioRxiv : the preprint server for biology · 2026Article
- Is there a role for apolipoprotein E in perinatal brain injury?Molecular and cellular pediatrics · 2026Review
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- The APOE4-estrogen-microglia axis in perimenopausal cognitive changes: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Assessing outer retinal and choroidal changes in scd: potential for high-risk screening using SS-OCTA.Translational psychiatry · 2025Article
- The connection between autophagy and Alzheimer's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therapeutic Perspectives-A Narrative Review.Brain sciences · 2025Review
- RSV Infection and Neurodegenerative Diseases: A Hypothesis of Energy Metabolism Disruption via the Lung-Brain Axis.Aging and disease · 2025Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alzheimer's disease (AD) is a predominant form of dementia in elderly. In sporadic AD and in families with higher risk of AD, correlation with apolipoprotein E4 (APOE) allele expression has been found. How APOE4 induces its pathological effects is still unclear. Several studies indicate that autophagy, a major degradation pathway trough the lysosome, may be compromised in AD. Here we studied, the effects of APOE isoforms expression in microglia cells. By using an in-situ model, the clearance of Aβ plaques from brain sections of transgenic 5xFAD mice by the APOE expressing microglia was examined. The results show that APOE4 microglia has Impairment In clearance of insoluble Aβ plaques as compared to APOE3 and APOE2 microglia. Furthermore, APOE4 affect the uptake of soluble Aβ. We found that microglia expressing APOE4 exhibit reduced autophagic flux as compared to those expressing APOE3. The autophagy inhibitor chloroquine also blocked Aβ plaque uptake in APOE3 expressing cells. Furthermore, we found that APOE4 expressing microglia have altered mitochondrial dynamics protein expression, mitochondrial morphology and mitochondrial activity compared to those expressing APOE2, and APOE3. Rapamycin treatment corrected Mitochondrial Membrane Potential in APOE4-expressing cells. Taken together, these findings suggest that APOE4 impairs the activation of autophagy, mitophagy, and Aβ clearance and that autophagy-inducing treatments, such as rapamycin, can enhance autophagy and mitochondrial functions in APOE4 expressing microglia. Our results reveal a direct link between APOE4 to autophagy activity in microglia, suggesting that the pathological effects of APOE4 could be counteracted by pharmacological treatments inducing autophagy, such as rapamycin.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.