ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
AAV2/1 CD74 Gene Transfer Reduces β-amyloidosis and Improves Learning and Memory in a Mouse Model of Alzheimer's Disease.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 41 citations in OpenAlex.
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- Single-cell transcriptome profiling highlights the role of APP in blood vessels in assessing the risk of patients with proliferative diabetic retinopathy developing Alzheimer's disease.Frontiers in cell and developmental biology · 2023Article
- Neurodegenerative Diseases: From Dysproteostasis, Altered Calcium Signalosome to Selective Neuronal Vulnerability to AAV-Mediated Gene Therapy.International journal of molecular sciences · 2022Review
- C5aR1 antagonism alters microglial polarization and mitigates disease progression in a mouse model of Alzheimer's disease.Acta neuropathologica communications · 2022Article
- Linking Oxidative Stress and Proteinopathy in Alzheimer's Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Differentially expressed genes in Alzheimer's disease highlighting the roles of microglia genes including OLR1 and astrocyte gene CDK2AP1.Brain, behavior, & immunity - health · 2021Article
- Targeting Age-Related Neurodegenerative Diseases by AAV-Mediated Gene Therapy.Advances in experimental medicine and biology · 2021Article
- HLA in Alzheimer's Disease: Genetic Association and Possible Pathogenic Roles.Neuromolecular medicine · 2020Review
- An Antisense Oligonucleotide Leads to Suppressed Transcription of Hdac2 and Long-Term Memory Enhancement.Molecular therapy. Nucleic acids · 2020Article
- Neurotrophic interactions between neurons and astrocytes following AAV1-Rheb(S16H) transduction in the hippocampus in vivo.British journal of pharmacology · 2020Article
- The future of gene-targeted therapy for hereditary tyrosinemia type 1 as a lead indication among the inborn errors of metabolism.Expert opinion on orphan drugs · 2020Article
- High-fat diet impairs cognitive function of zebrafish.Scientific reports · 2019Article
- Identifying and ranking potential driver genes of Alzheimer's disease using multiview evidence aggregation.Bioinformatics (Oxford, England) · 2019Article
- Characteristics and advantages of adeno-associated virus vector-mediated gene therapy for neurodegenerative diseases.Neural regeneration research · 2019Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Modulation of the amyloid-β (Aβ) trafficking pathway heralds a new therapeutic frontier for Alzheimer's disease (AD). As CD74 binds to the amyloid-β precursor protein (APP) and can suppresses Aβ processing, we investigated whether recombinant adeno-associated virus (AAV) delivery of CD74 could reduce Aβ production and affect disease outcomes. This idea was tested in a mouse AD model. Cotransduction of AAV-tetracycline-controlled transactivator (tTA) and AAV-tet-response element (TRE)-CD74 resulted in CD74 expression, reduced Aβ production in mouse neurons containing the human APP with familial AD-linked mutations. Stereotaxic injection of AAV-TRE-GFP or CD74 into the hippocampi of an AD mouse, defined as a TgCRND8 × calmodulin-dependent protein kinase II derived promoter-tTA double-transgenic, reduced Aβ loads and pyramidal neuronal Aβ accumulation in the hippocampus. Immunofluorescent studies showed that APP colocalization with Lamp1 was increased in CD74-expressing neurons. Moreover, Morris water maze tasks demonstrated that mice treated with AAV-TRE-CD74 showed improved learning and memory compared to AAV-TRE-GFP control animals. These results support the idea that CD74-induced alteration of Aβ processing could improve AD-associated memory deficits as shown in mouse models of human disease.
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