ArticleProceedings of the National Academy of Sciences of the United States of America2011
FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disorders.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 147 citations in OpenAlex.
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- FGF family in health and disease.Molecular biomedicine · 2026Review
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- FGF-FGFR Signaling in Parkinson's Disease: Mechanistic Links to Ferroptosis and Neuroprotection.Brain sciences · 2026Review
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- Plasma FGF2 and YAP1 as novel biomarkers for MCI in the elderly: analysis via bioinformatics and clinical study.Frontiers in neuroscience · 2025Article
- Unraveling the Intricacies: The Role of miRNAs in the Progression and Initiation of Alzheimer's Disease.Current Alzheimer research · 2025Article
- Extracellular Vesicles Derived from FGF2-Primed Astrocytes Against Mitochondrial and Synaptic Toxicities in Parkinson's Disease.International journal of nanomedicine · 2025Article
- Neurotrophic factor-α1/carboxypeptidase E controls progression and reversal of Alzheimer's disease pathogenesis in mice.Theranostics · 2025Article
- Diversity of Microglia-Derived Molecules with Neurotrophic Properties That Support Neurons in the Central Nervous System and Other Tissues.Molecules (Basel, Switzerland) · 2024Review
- Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.Molecular neurodegeneration · 2024Article
- Physical Exercise Counteracts Aging-Associated White Matter Demyelination Causing Cognitive Decline.Aging and disease · 2024Review
- Growth Factors and Their Application in the Therapy of Hereditary Neurodegenerative Diseases.Biomedicines · 2024Review
- Multi-analyte proteomic analysis identifies blood-based neuroinflammation, cerebrovascular and synaptic biomarkers in preclinical Alzheimer's disease.medRxiv : the preprint server for health sciences · 2024Article
- Agomirs upregulating carboxypeptidase E expression rescue hippocampal neurogenesis and memory deficits in Alzheimer's disease.Translational neurodegeneration · 2024Article
- The concept of resilience to Alzheimer's Disease: current definitions and cellular and molecular mechanisms.Molecular neurodegeneration · 2024Review
- Involvement of Fgf2-mediated tau protein phosphorylation in cognitive deficits induced by sevoflurane in aged rats.Molecular medicine (Cambridge, Mass.) · 2024Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The adult hippocampus plays a central role in memory formation, synaptic plasticity, and neurogenesis. The subgranular zone of the dentate gyrus contains neural progenitor cells with self-renewal and multilineage potency. Transgene expression of familial Alzheimer's disease-linked mutants of β-amyloid precursor protein (APP) and presenilin-1 leads to a significant inhibition of neurogenesis, which is potentially linked to age-dependent memory loss. To investigate the effect of neurogenesis on cognitive function in a relevant disease model, FGF2 gene is delivered bilaterally to the hippocampi of APP+presenilin-1 bigenic mice via an adenoassociated virus serotype 2/1 hybrid (AAV2/1-FGF2). Animals injected with AAV2/1-FGF2 at a pre- or postsymptomatic stage show significantly improved spatial learning in the radial arm water maze test. A neuropathological investigation demonstrates that AAV2/1-FGF2 injection enhances the number of doublecortin, BrdU/NeuN, and c-fos-positive cells in the dentate gyrus, and the clearance of fibrillar amyloid-β peptide (Aβ) in the hippocampus. AAV2/1-FGF2 injection also enhances long-term potentiation in another APP mouse model (J20) compared with control AAV2/1-GFP-injected littermates. An in vitro study confirmed the enhanced neurogenesis of mouse neural stem cells by direct AAV2/1-FGF2 infection in an Aβ oligomer-sensitive manner. Further, FGF2 enhances Aβ phagocytosis in primary cultured microglia, and reduces Aβ production from primary cultured neurons after AAV2/1-FGF2 infection. Thus, our data indicate that virus-mediated FGF2 gene delivery has potential as an alternative therapy of Alzheimer's disease and possibly other neurocognitive disorders.
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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.