ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
AAV-mediated neuronal expression of an scFv antibody selective for Aβ oligomers protects synapses and rescues memory in Alzheimer models.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Preclinical evaluation of AAV2 anti-VEGF gene therapy using scFv for choroidal neovascularization.Molecular therapy. Advances · 2026Article
- Use of high-affinity scFv antibody NUsc1 for isolation and sensitive detection of Alzheimer's-associated amyloid beta oligomers.The Journal of biological chemistry · 2026Article
- AAV-mediated gene therapy for Alzheimer's disease: neuroprotective mechanisms and translational challenges.Frontiers in aging neuroscience · 2026Review
- Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Viral and non-viral cellular therapies for neurodegeneration.Frontiers in medicine · 2025Review
- Significance of gene therapy in neurodegenerative diseases.Frontiers in neuroscience · 2025Review
- The promise of gene therapy in common types of dementia.BioImpacts : BI · 2025Review
- Discovery of Potential Drug Targeting Key Genes in Alzheimer's Disease: Insights from Transcriptome Analysis and Molecular Docking.Journal of molecular neuroscience : MN · 2024Article
- Recombinant Antibody Fragments for Immunotherapy of Parkinson's Disease.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Amyloid Precursor Protein: A Regulatory Hub in Alzheimer's Disease.Aging and disease · 2024Review
- The Potential of Single-Chain Variable Fragment Antibody: Role in Future Therapeutic and Diagnostic Biologics.Journal of immunology research · 2024Review
- Recombinant Antibody Fragments for Neurological Disorders: An Update.Current neuropharmacology · 2024Review
- Oxytocin attenuates microglial activation and restores social and non-social memory in APP/PS1 Alzheimer model mice.iScience · 2023Article
Corrections and comments
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Authors and funding
24 authors at 10 institutions in 6 countries.
Funding
Abstract
The accumulation of soluble oligomers of the amyloid-β peptide (AβOs) in the brain has been implicated in synapse failure and memory impairment in Alzheimer's disease. Here, we initially show that treatment with NUsc1, a single-chain variable-fragment antibody (scFv) that selectively targets a subpopulation of AβOs and shows minimal reactivity to Aβ monomers and fibrils, prevents the inhibition of long-term potentiation in hippocampal slices and memory impairment induced by AβOs in mice. As a therapeutic approach for intracerebral antibody delivery, we developed an adeno-associated virus vector to drive neuronal expression of NUsc1 (AAV-NUsc1) within the brain. Transduction by AAV-NUsc1 induced NUsc1 expression and secretion in adult human brain slices and inhibited AβO binding to neurons and AβO-induced loss of dendritic spines in primary rat hippocampal cultures. Treatment of mice with AAV-NUsc1 prevented memory impairment induced by AβOs and, remarkably, reversed memory deficits in aged APPswe/PS1ΔE9 Alzheimer's disease model mice. These results support the feasibility of immunotherapy using viral vector-mediated gene delivery of NUsc1 or other AβO-specific single-chain antibodies as a potential therapeutic approach in Alzheimer's disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.