Version history

{
  "field_tag": "astrocytes",
  "text": "What resolves this contention: APOE4 drives AD pathology through gain-of-toxic-function: early apoE4 overexpression strongly increases plaque load, apoE4 particles are abnormally large, and APOE4 has broad detrimental effects on tau, microglia, and astrocyte reactivity beyond amyloid-β vs. APOE4 effects may partly reflect loss-of-function: apoE4 has reduced half-life, constitutes only 30–40% of total apoE in heterozygous mice, and ASO-mediated APOE suppression reduces plaques, suggesting reducing apoE (including apoE4) is beneficial / APOE ε4 allele remains the strongest genetic risk factor for sporadic Alzheimer's disease, with pathogenic mechanisms now understood to extend beyond amyloid-β to include tau neurodegeneration, microglia and astrocyte responses, and blood-brain barrier disruption. / In targeted replacement APOE3/4 mice, apoE4 constitutes only 30–40% of total apoE levels due to enhanced degradation and re",
  "source_refs": [
    "paper:paper-c05fea99dd6f",
    "paper:paper-d74c3cfc15b9",
    "wiki_page:computationalreviewastrocytes-12",
    "paper:paper-c05fea99dd6f",
    "paper:paper-d74c3cfc15b9",
    "wiki_page:computationalreviewastrocytes-12",
    "paper:paper-c05fea99dd6f",
    "paper:paper-d74c3cfc15b9",
    "wiki_page:computationalreviewastrocytes-12",
    "paper:paper-c05fea99dd6f",
    "paper:paper-d74c3cfc15b9",
    "wiki_page:computationalreviewastrocytes-12"
  ],
  "importance": "0.7200",
  "tractability": "0.5500",
  "potential_impact": "0.7000",
  "composite_score": "0.2772",
  "elo_rating": "1500.00",
  "state": "open",
  "decay_rate": "0.01000",
  "resolution_evidence_refs": []
}