ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
AAVrh.10 delivery of novel APOE2-Christchurch variant suppresses amyloid and Tau pathology in Alzheimer's disease mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Protective mutations associated with APOE in Alzheimer's disease.Molecular psychiatry · 2026Review
- Consequences of human genetic variations inMolecular therapy. Advances · 2026Article
- Alzheimer disease protection from the periphery.Nature reviews. Neurology · 2026Article
- Advancements in Gene Delivery using Nucleic Acid Loaded Nanoparticles for Region Specific Delivery in Alzheimer's Disease.Molecular neurobiology · 2026Review
- Review
- Astrocytic APOE3-Christchurch expression ameliorates brain amyloid-β pathology in 5xFAD mice.Translational psychiatry · 2026Article
- APOE3-Christchurch variant enhances neurovascular support functions of iPSC-derived mesenchymal stromal cells.Frontiers in molecular biosciences · 2026Article
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- AAV-mediated gene therapy for Alzheimer's disease: neuroprotective mechanisms and translational challenges.Frontiers in aging neuroscience · 2026Review
- APOE Lipoprotein Particles: Pathophysiology, Therapy, and the Crosstalk in Alzheimer's Disease and Cardiovascular Disease.Molecular neurobiology · 2025Review
- APOE-Targeted Therapeutics for Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Review
- The Christchurch point mutation in mouse APOE reduces Aβ-induced tau and α-synuclein pathologies.bioRxiv : the preprint server for biology · 2025Article
- Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.Molecular therapy. Nucleic acids · 2025Review
- Apolipoprotein E in Alzheimer's disease: molecular insights and therapeutic opportunities.Molecular neurodegeneration · 2025Review
- Viral vectors in neurodegenerative diseases: immune responses and therapeutic applications.Frontiers in neurology · 2025Review
- The role of lipid metabolism in cognitive impairment.Arquivos de neuro-psiquiatria · 2025Review
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8 authors.
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Abstract
Gene therapy to treat hereditary disorders conventionally delivers the normal allele to compensate for loss-of-function mutations. More effective gene therapy may be achieved using a gain-of-function variant. We tested the hypothesis that AAVrh.10-mediated CNS delivery of the human APOE2 allele with the Christchurch mutation (R136S) (E2Ch) will provide superior protection against APOE4-associated Alzheimer's disease (AD) in mice compared to the unmodified APOE2 allele (E2). The vectors were assessed in two mouse strains with humanized APOE4: APP.PSEN1/TRE4 "amyloid mice" and P301S/TRE4, "tau mice." Both the E2Ch and E2 vectors prevented Aβ42 and Aβ40 accumulation and decreased β-amyloid aggregates in amyloid mice, but only the E2Ch vector suppressed tau tangles in tau mice. Microglial activation and reactive astrocytes were significantly suppressed by both vectors in amyloid mice but only the E2Ch vector mediated significant suppression of Iba1 and glial fibrillary acidic protein (GFAP) in tau mice. In four behavioral assays, the E2 and E2Ch vectors had similar benefits in amyloid mice, but E2Ch outperformed E2 in tau mice. In summary, while E2 is effective in suppressing amyloid pathology, the novel E2 variant E2Ch more effectively treats both the amyloid and tau pathology of murine AD in APOE4 background, supporting the development of AAVrh.10APOE2Ch as a therapy for APOE4-associated AD.
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