ArticleActa neuropathologica communications2019
APOE genotype and sex affect microglial interactions with plaques in Alzheimer's disease mice.
Article in Acta neuropathologica communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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Who cites it
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- Transcriptional landscape of human microglia implicates age, sex, and APOE-related immunometabolic pathway perturbations.Aging cell · 2022Pooled it
- Does sex moderate health and Alzheimer's disease risk tied to early educational experiences? The reducing inequities through social and educational change follow-up in early adulthood extension study protocol.Brain, behavior, & immunity - health · 2026Article
- APOEε4 attenuates early TREM2-mediated microglial responses and influences disease trajectories in dementia with Lewy bodies.Research square · 2026Article
- Sex-dependent interferon signaling contributes to female-biased vulnerability in Alzheimer's disease.Journal of neuroinflammation · 2026Article
- Glial pathology networks reveal early olfactory vulnerability in post mortem human Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Article
- Non-compacted, PET-insensitive amyloid states increase after systemic inflammation and predict neuritic damage across Aβ pathology models and Alzheimer patients.Research square · 2026Article
- Sex and gender-related differences in neurological diseases: current challenges and recommendations for clinical practice.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026Review
- Update on sex-specific microglia contribution to early synaptic dysfunction in Alzheimer's disease.Frontiers in molecular neuroscience · 2026Review
- Behavioral deficits and exacerbated neural and hemodynamic odor responses during lifespan of a mouse model of late onset Alzheimer's disease expressing humanized APOEε4 and Trem2*R47H.Frontiers in aging neuroscience · 2026Article
- Microglial interferon signaling and Aβ plaque pathology are enhanced in female 5xFAD Alzheimer's disease mice, independent of estrous cycle stage.Journal of neuroinflammation · 2025Article
- Roles of TREM2 in Alzheimer's disease.Translational neurodegeneration · 2025Review
- The connection between autophagy and Alzheimer's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Review
- The APOE-Microglia Axis in Alzheimer's Disease: Functional Divergence and Therapeutic Perspectives-A Narrative Review.Brain sciences · 2025Review
- Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17α-estradiol in middle-aged male mice.Communications medicine · 2025Article
- Sex/gender effects of glial reactivity on preclinical Alzheimer's disease pathology.Molecular psychiatry · 2025Article
- Article
- APOE from astrocytes restores Alzheimer's Aβ-pathology and DAM-like responses in APOE deficient microglia.EMBO molecular medicine · 2024Article
- Role of the gut microbiome in mediating sex-specific differences in the pathophysiology of Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Microglia affect Alzheimer's disease (AD) pathogenesis in opposing manners, by protecting against amyloid accumulation in early phases of the disease and promoting neuropathology in advanced stages. Recent research has identified specific microglial interactions with amyloid plaques that exert important protective functions including attenuation of early pathology. It is unknown how these protective microglial interactions with plaques are affected by apolipoprotein E (APOE) genotype and sex, two well-established AD risk factors that modulate microglial function. We investigated this question using quantitative confocal microscopy to compare microglial interactions with amyloid plaques in male and female EFAD mice across APOE3 and APOE4 genotypes at 6 months of age. We observed that microglial coverage of plaques is highest in male APOE3 mice with significant reductions in coverage observed with both APOE4 genotype and female sex. Plaque compaction, a beneficial consequence of microglial interactions with plaques, showed a similar pattern in which APOE4 genotype and female sex were associated with significantly lower values. Within the plaque environment, microglial expression of triggering receptor expressed on myeloid cells 2 (TREM2), a known regulator of microglial plaque coverage, was highest in male APOE3 mice and reduced by APOE4 genotype and female sex. These differences in plaque interactions were unrelated to the number of microglial processes in the plaque environment across groups. Interestingly, the pattern of amyloid burden across groups was opposite to that of microglial plaque coverage, with APOE4 genotype and female sex showing the highest amyloid levels. These findings suggest a possible mechanism by which microglia may contribute to the increased AD risk associated with APOE4 genotype and female sex.
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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.