ArticleMolecular neurodegeneration2023
APOE effects on regional tau in preclinical Alzheimer's disease.
Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 67 citations in OpenAlex.
- Article
- Docosahexaenoic acid remodels lipid composition of lipid rafts and mitochondrial function in ApoE4/4 mouse brain: a multi-omic investigation.Molecular biomedicine · 2026Article
- Global and regional amyloid-β in explaining APOE-ε4 and sex associations with medial temporal tau: a neuropathology study.Acta neuropathologica · 2026Article
- Genetic Determinants of Tau-PET Imaging in Alzheimer's Disease: A Narrative Review of Genome-Wide and Candidate-Gene Studies.Journal of imaging · 2026Review
- Review
- Orthogonal Contributions of Genetic, Clinical, and Social Determinants of Health Risk Burdens on Alzheimer's Disease Pathophysiology.medRxiv : the preprint server for health sciences · 2026Article
- Spatiotemporal dynamics of tau extent and load increase in Alzheimer's disease across four longitudinal cohorts.Nature aging · 2026Article
- Subtyping and staging of Alzheimer's disease from routine structural MRI with PHASE-AD.medRxiv : the preprint server for health sciences · 2026Article
- Multi-domain AD risk burden and plasma biomarkers in cognitively unimpaired adults.medRxiv : the preprint server for health sciences · 2026Article
- Contributions of the Alzheimer's Disease Neuroimaging Initiative to advancing AD research: a targeted review of recent publications.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Life's Essential 8, genetic susceptibility, and risk of cognitive impairment: results from an elder population-based cohort study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- Plasma p-tau217 assays effectively predict amyloid status but lack precision for tau staging in Alzheimer's disease.Journal of neurology · 2026Article
- APOE genotype differentially modulates prion pathology in a mouse model.Acta neuropathologica communications · 2026Article
- Modeling neurovascular dysfunction in Alzheimer's disease using an isogenic brain-chip model.Fluids and barriers of the CNS · 2026Article
- Common and rare variant analyses implicateNPJ dementia · 2026Article
- Spatial patterns of tau accumulation across the Alzheimer's disease spectrum.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- APOE Genotype Differentially Modulates Prion Pathology in a Mouse Model.Research square · 2025Article
- Poor dream recall associates with Alzheimer's disease biomarkers and dementia risk.medRxiv : the preprint server for health sciences · 2025Article
- Apolipoprotein E Alleles and Motor Signs in Older Adults with Alzheimer's Dementia.International journal of molecular sciences · 2025Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundAPOE variants are strongly associated with abnormal amyloid aggregation and additional direct effects of APOE on tau aggregation are reported in animal and human cell models. The degree to which these effects are present in humans when individuals are clinically unimpaired (CU) but have abnormal amyloid (Aβ+) remains unclear.
methodsWe analyzed data from CU individuals in the Anti-Amyloid Treatment in Asymptomatic AD (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies. Amyloid PET data were available for 4486 participants (3163 Aβ-, 1323 Aβ+) and tau PET data were available for a subset of 447 participants (55 Aβ-, 392 Aβ+). Linear models examined APOE (number of e2 and e4 alleles) associations with global amyloid and regional tau burden in medial temporal lobe (entorhinal, amygdala) and early neocortical regions (inferior temporal, inferior parietal, precuneus). Consistency of APOE4 effects on regional tau were examined in 220 Aβ + CU and mild cognitive impairment (MCI) participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI).
resultsAPOE2 and APOE4 were associated with lower and higher amyloid positivity rates, respectively. Among Aβ+ CU, e2 and e4 were associated with reduced (-12 centiloids per allele) and greater (+15 centiloids per allele) continuous amyloid burden, respectively. APOE2 was associated with reduced regional tau in all regions (-0.05 to -0.09 SUVR per allele), whereas APOE4 was associated with greater regional tau (+0.02 to +0.07 SUVR per allele). APOE differences were confirmed by contrasting e3/e3 with e2/e3 and e3/e4. Mediation analyses among Aβ+ s showed that direct effects of e2 on regional tau were present in medial temporal lobe and early neocortical regions, beyond an indirect pathway mediated by continuous amyloid burden. For e4, direct effects on regional tau were only significant in medial temporal lobe. The magnitude of protective e2 effects on regional tau was consistent across brain regions, whereas detrimental e4 effects were greatest in medial temporal lobe. APOE4 patterns were confirmed in Aβ+ ADNI participants.
conclusionsAPOE influences early regional tau PET burden, above and beyond effects related to cross-sectional amyloid PET burden. Therapeutic strategies targeting underlying mechanisms related to APOE may modify tau accumulation among Aβ+ individuals.
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