ArticleScientific reports2021
Astrocytic expression of the Alzheimer's disease risk allele, ApoEε4, potentiates neuronal tau pathology in multiple preclinical models.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Intranasal drug delivery to the brain for neurodegenerative diseases: Current efforts and challenges in delivery platforms and modeling.Advanced drug delivery reviews · 2026Review
- Traumatic Brain Injury and the Road to Alzheimer's Disease.Biomedicines · 2026Review
- Review
- Should ApoE4 gene editing therapy be approached with caution when AD is accompanied by retinal neurodegenerative diseases?Frontiers in neurology · 2026Review
- Dual inhibition of IRAK1/TAK1 signaling in astrocytes reduces accelerated mortality in human APOE4 knock-in APPswe/PSEN1dE9/P301S-Tau triple transgenic mouse model.Journal of neuroinflammation · 2025Article
- Advances of therapeutic strategies for Alzheimer's disease.Journal of neurology · 2025Review
- Article
- Inhibition of Bone Morphogenetic Protein Signaling Prevents Tau Pathology in iPSC Derived Neurons and PS19 Mice.Annals of neurology · 2025Article
- Astrocytes Lingering at a Crossroads: Neuroprotection and Neurodegeneration in Neurocognitive Dysfunction.International journal of biological sciences · 2025Review
- Comprehensive Overview of Alzheimer's Disease: Etiological Insights and Degradation Strategies.International journal of molecular sciences · 2024Review
- Astrocyte-Neuron Interactions in Alzheimer's Disease.Advances in neurobiology · 2024Review
- Glial-derived mitochondrial signals affect neuronal proteostasis and aging.Science advances · 2023Article
- Roles of ApoE4 on the Pathogenesis in Alzheimer's Disease and the Potential Therapeutic Approaches.Cellular and molecular neurobiology · 2023Review
- Tau and neuroinflammation in Alzheimer's disease: interplay mechanisms and clinical translation.Journal of neuroinflammation · 2023Review
- Chemotherapy promotes astrocytic response to Aβ deposition, but not Aβ levels, in a mouse model of amyloid and APOE.Neurobiology of disease · 2022Article
- APOE in the bullseye of neurodegenerative diseases: impact of the APOE genotype in Alzheimer's disease pathology and brain diseases.Molecular neurodegeneration · 2022Review
- Network Tau spreading is vulnerable to the expression gradients ofScience translational medicine · 2022Article
- Chimeric cerebral organoids reveal the essentials of neuronal and astrocytic APOE4 for Alzheimer's tau pathology.Signal transduction and targeted therapy · 2022Article
- Transgenic Mouse Models of Alzheimer's Disease: An Integrative Analysis.International journal of molecular sciences · 2022Review
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ApoEε4 is a major genetic risk factor for Alzheimer's disease (AD), a disease hallmarked by extracellular amyloid-beta (Aβ) plaques and intracellular neurofibrillary tangles (NFTs). The presence of the ApoEε4 allele is associated with increased Aβ deposition and a role for ApoEε4 in the potentiation of tau pathology has recently emerged. This study focused on comparing the effects of adeno-associated virus (AAV)-mediated overexpression of the three predominant human ApoE isoforms within astrocytes. The isoform-specific effects of human ApoE were evaluated within in vitro models of tau pathology within neuron/astrocyte co-cultures, as well as in a transgenic tau mouse model. Tau aggregation, accumulation, and phosphorylation were measured to determine if the three isoforms of human ApoE had differential effects on tau. Astrocytic overexpression of the human ApoEε4 allele increased phosphorylation and misfolding of overexpressed neuronal tau in multiple models, including the aggregation and accumulation of added tau oligomers, in an isoform-specific manner. The ability of ApoEε4 to increase tau aggregation could be inhibited by an ApoEε4-specific antibody. This study indicates that astrocytic expression of ApoEε4 can potentiate tau aggregation and phosphorylation within neurons and supports a gain of toxic function hypothesis for the effect of hApoEε4 on tau.
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