ArticleThe Journal of clinical investigation2023
APOE-ε4 synergizes with sleep disruption to accelerate Aβ deposition and Aβ-associated tau seeding and spreading.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
- Sleep complaints and genetic risk of Alzheimer's disease in older women: associations with memory and tau deposition.The journal of prevention of Alzheimer's disease · 2026Article
- Dual orexin receptor antagonism with lemborexant enhances microglial clearance of β-amyloid in mice.Molecular neurodegeneration · 2026Article
- Diurnal choroid plexus function in mice depends on sex, age, and amyloid-β status.Communications biology · 2026Article
- Implication of the thalamus in sleep alterations observed in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- The Function of Microglia in Cognitive Impairment Influenced by Sleep Deprivation.Cellular and molecular neurobiology · 2026Review
- Astrocyte-blood-brain barrier crosstalk in cerebral small vessel disease: linking barrier dysfunction to neurovascular failure.Frontiers in neurology · 2026Review
- Mechanistic role of APOE lipidation in Alzheimer's disease pathogenesis.Theranostics · 2026Review
- Aquaporin-4 mis-localization decreases glymphatic clearance of α-synuclein in an alpha-syntrophin knock out mouse model and promotes α-synuclein pathology and aggregate propagation.Brain communications · 2026Article
- Effects of acute sleep deprivation on individuals across differentFrontiers in neurology · 2026Article
- APOE Genotype Difference in the Biphasic Modulation of Amyloid-β Aggregation by Direct Binding and Lowering the Nucleation Barrier.Biomacromolecules · 2025Article
- Glymphatic system dysfunction mediates amyloid deposition and cognitive impairment in Alzheimer's disease: a PET/MRI multimodality imaging study.EJNMMI research · 2025Article
- Subjective sleep characteristics in non-demented adults: domain-specific associations with multimodal Alzheimer's disease biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Circadian rhythms and the light-dark cycle interact to regulate amyloid-beta plaque accumulation and tau phosphorylation in 5xFAD mice.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- HSV-1 hijacks mitochondrial dynamics: potential molecular mechanisms linking viral infection to neurodegenerative disorders.Apoptosis : an international journal on programmed cell death · 2025Review
- APOE deficiency inhibits amyloid-facilitated (A) tau pathology (T) and neurodegeneration (N), halting progressive ATN pathology in a preclinical model.Molecular psychiatry · 2025Article
- Periventricular diffusivity reflects APOE ε4-modulated amyloid accumulation and cognitive impairment in the Alzheimer's disease continuum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Sleep quality, APOE ε4, and Alzheimer's disease: associations from two prospective cohort studies and mechanisms by plasma proteomic analysis.BMC medicine · 2025Article
- Circadian rhythms and the light-dark cycle interact to regulate amyloid plaque accumulation and tau phosphorylation in 5xFAD mice.bioRxiv : the preprint server for biology · 2025Article
- Pathological mechanisms and treatment progression of Alzheimer's disease.European journal of medical research · 2025Review
- Lower slow wave sleep and rapid eye movement sleep are associated with brain atrophy of Alzheimer's disease-vulnerable regions.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025Article
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9 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is the most common cause of dementia. The APOE-ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset AD. The APOE genotype modulates the effect of sleep disruption on AD risk, suggesting a possible link between apoE and sleep in AD pathogenesis, which is relatively unexplored. We hypothesized that apoE modifies Aβ deposition and Aβ plaque-associated tau seeding and spreading in the form of neuritic plaque-tau (NP-tau) pathology in response to chronic sleep deprivation (SD) in an apoE isoform-dependent fashion. To test this hypothesis, we used APPPS1 mice expressing human APOE-ε3 or -ε4 with or without AD-tau injection. We found that SD in APPPS1 mice significantly increased Aβ deposition and peri-plaque NP-tau pathology in the presence of APOE4 but not APOE3. SD in APPPS1 mice significantly decreased microglial clustering around plaques and aquaporin-4 (AQP4) polarization around blood vessels in the presence of APOE4 but not APOE3. We also found that sleep-deprived APPPS1:E4 mice injected with AD-tau had significantly altered sleep behaviors compared with APPPS1:E3 mice. These findings suggest that the APOE-ε4 genotype is a critical modifier in the development of AD pathology in response to SD.
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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.