ArticleActa neuropathologica communications2023
Humanized APOE genotypes influence lifespan independently of tau aggregation in the P301S mouse model of tauopathy.
Article in Acta neuropathologica communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.Journal of neurology · 2025Pooled it
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- Cell apoptosis in ischemic stroke: Focus on lipid metabolism.Neural regeneration research · 2026Article
- Review
- A critical appraisal of the link between apolipoprotein E and Tau.Current opinion in neurology · 2026Review
- Olfactory-Guided Behavior Uncovers Imaging and Molecular Signatures of Alzheimer's Disease Risk.Brain sciences · 2025Article
- Smelling the Risk: Early Olfactory Deficits, Brain Networks, and Blood Markers of Alzheimer's Disease Risk in Humanized APOE Mice.bioRxiv : the preprint server for biology · 2025Article
- Noninvasive Detection of Oxidative Stress in a Mouse Model of 4R Tauopathy via Positron Emission Tomography with [International journal of molecular sciences · 2025Article
- Microglia depletion reduces human neuronal APOE4-related pathologies in a chimeric Alzheimer's disease model.Cell stem cell · 2025Article
- Repetitive head trauma and apoE4 induce chronic cerebrovascular alterations that impair tau elimination from the brain.Experimental neurology · 2024Article
- Feature attention graph neural network for estimating brain age and identifying important neural connections in mouse models of genetic risk for Alzheimer's disease.Imaging neuroscience (Cambridge, Mass.) · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
Apolipoprotein (APOE) E4 isoform is a major risk factor of Alzheimer's disease and contributes to metabolic and neuropathological abnormalities during brain aging. To provide insights into whether APOE4 genotype is related to tau-associated neurodegeneration, we have generated human P301S mutant tau transgenic mice (PS19) that carry humanized APOE alleles (APOE2, APOE3 or APOE4). In aging mice that succumbed to paralysis, PS19 mice homozygous for APOE3 had the longest lifespan when compared to APOE4 and APOE2 homozygous mice (APOE3 > APOE4 ~ APOE2). Heterozygous mice with one human APOE and one mouse Apoe allele did not show any variations in lifespan. At end-stage, PS19 mice homozygous for APOE3 and APOE4 showed equivalent levels of phosphorylated tau burden, inflammation levels and ventricular volumes. Compared to these cohorts, PS19 mice homozygous for APOE2 showed lower induction of phosphorylation on selective epitopes, though the effect sizes were small and variable. In spite of this, the APOE2 cohort showed shorter lifespan relative to APOE3 homozygous mice. None of the cohorts accumulated appreciable levels of phosphorylated tau compartmentalized in the insoluble cell fraction. RNAseq analysis showed that the induction of immune gene expression was comparable across all the APOE genotypes in PS19 mice. Notably, the APOE4 homozygous mice showed additional induction of transcripts corresponding to the Alzheimer's disease-related plaque-induced gene signature. In human Alzheimer's disease brain tissues, we found no direct correlation between higher burden of phosphorylated tau and APOE4 genotype. As expected, there was a strong correlation between phosphorylated tau burden with amyloid deposition in APOE4-positive Alzheimer's disease cases. Overall, our results indicate that APOE3 genotype may confer some resilience to tauopathy, while APOE4 and APOE2 may act through multiple pathways to increase the pathogenicity in the context of tauopathy.
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