ArticleMolecular psychiatry2014
APOE2 enhances neuroprotection against Alzheimer's disease through multiple molecular mechanisms.
Article in Molecular psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Chronic Cerebral Hypoxia and Cognitive Impairment: A Systematic Review and Meta-Analysis Based on Chronic Mountain Sickness, Anemia, Chronic Obstructive Pulmonary Disease, and Obstructive Sleep Apnea.CNS neuroscience & therapeutics · 2026Pooled it
- Longevity and cognitive resilience in a Colombian family carrying theJournal of Alzheimer's disease : JAD · 2026Article
- Syndrome-specific vulnerability of neuronal and glial 4-repeat frontotemporal lobar degeneration-tau.Brain : a journal of neurology · 2026Article
- Vulnerability of anterior cingulate Von Economo neurons to FTLD-tauopathies in behavioral variant frontotemporal dementia.Cerebral cortex (New York, N.Y. : 1991) · 2026Article
- Association between Alzheimer's disease-related genes and neurodegenerative blood-based biomarkers in Indian adults.Frontiers in aging neuroscience · 2026Article
- Sex andInternational journal of molecular sciences · 2025Article
- Cerebrospinal fluid proteomic associations of APOE genotypes reveal distinct protective and risk mechanisms for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Clinical Significance of APOE4 Genotyping: Potential for Personalized Therapy and Early Diagnosis of Alzheimer's Disease.Journal of clinical medicine · 2025Review
- Nanoparticles as an Encouraging Therapeutic Approach to Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Regenerative Medicine in the Treatment of Alzheimer's Disease: A Narrative Review.Iranian journal of public health · 2025Review
- APOE and Alzheimer's disease and related dementias risk among 12,221 Hispanics/Latinos.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Physical activity andmedRxiv : the preprint server for health sciences · 2025Article
- Progress in AAV-Mediated In Vivo Gene Therapy and Its Applications in Central Nervous System Diseases.International journal of molecular sciences · 2025Review
- Resilience mechanisms underlying Alzheimer's disease.Metabolic brain disease · 2025Review
- Stools from a human APOEe2 donor reduces amyloid and tau pathology and increases neuroinflammation in a 3xTg AD mouse model.Frontiers in aging neuroscience · 2025Article
- APOE from astrocytes restores Alzheimer's Aβ-pathology and DAM-like responses in APOE deficient microglia.EMBO molecular medicine · 2024Article
- Prevalence of ApoE Alleles in a Spanish Population of Patients with a Clinical Diagnosis of Alzheimer's Disease: An Observational Case-Control Study.Medicina (Kaunas, Lithuania) · 2024Observational
- Analysis of early effects of human APOE isoforms on Alzheimer's disease and type III hyperlipoproteinemia pathways using knock-in rat models with humanized APP and APOE.Cell communication and signaling : CCS · 2024Article
- Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer's disease.Nature communications · 2024Article
- Lipoprotein Particles in Cerebrospinal Fluid.Arteriosclerosis, thrombosis, and vascular biology · 2024Review
40 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
Abstract
The common APOE2 gene variant is neuroprotective against Alzheimer's disease (AD) and reduces risk by nearly 50%. However, the mechanisms by which APOE2 confers neuroprotection are largely unknown. Here we showed that ApoE protein abundance in human postmortem cortex follows an isoform-dependent pattern (E2>E3>E4). We also identified a unique downstream transcriptional profile determined by microarray and characterized by downregulation of long-term potentiation (LTP) related transcripts and upregulation of extracellular matrix (ECM)/integrin-related transcripts in E2 cases and corroborated this finding at the protein level by demonstrating increases in ECM collagens and laminins. In vivo studies of healthy older individuals demonstrated a unique and advantageous biomarker signature in E2 carriers. APOE2 also reduced the risk of mild cognitive impairment to AD conversion by half. Our findings suggest that ApoE2 protein abundance, coupled with its inability to bind to LDLRs, may act to increase amyloid-beta (Ab) clearance. In addition, increased ECM and reduced LTP-related expression results in diminished activity-dependent Ab secretion and/or excitotoxicity, and thus also promotes neuroprotection.
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