ArticlePloS one2019
Cell-autonomous and non-cell autonomous effects of neuronal BIN1 loss in vivo.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Microglial Phagocytosis: A Disease-Associated Process Emerging from Alzheimer's Disease Genetics.Trends in neurosciences · 2020Pooled it
- AAV Vector-Mediated Modulation of Signaling Pathways in Neurological Disorders: Insights From Cellular, Animal, and Human Studies.Cell biochemistry and function · 2026Review
- Bridging autophagy and endolysosomal dysfunction: Role of bridging integrator 1 in Alzheimer's disease.Neural regeneration research · 2026Article
- Article
- BIN1Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The Cleavage-Specific Tau 12A12mAb Exerts an Anti-Amyloidogenic Action by Modulating the Endocytic and Bioenergetic Pathways in Alzheimer's Disease Mouse Model.International journal of molecular sciences · 2023Article
- Loss of forebrain BIN1 attenuates hippocampal pathology and neuroinflammation in a tauopathy model.Brain : a journal of neurology · 2023Article
- Pathogenesis of Chronic Kidney Disease Is Closely Bound up with Alzheimer's Disease, Especially via the Renin-Angiotensin System.Journal of clinical medicine · 2023Review
- Genetic polymorphism in BIN1 rather than APOE is associated with poor recognition memory among men without dementia.Scientific reports · 2022Article
- The role of Alzheimer's disease risk genes in endolysosomal pathways.Neurobiology of disease · 2022Review
- Therapeutically viable generation of neurons with antisense oligonucleotide suppression of PTB.Nature neuroscience · 2021Article
- Alzheimer's disease brain-derived extracellular vesicles spread tau pathology in interneurons.Brain : a journal of neurology · 2021Article
- Serious neonatal morbidities are associated with differences in DNA methylation among very preterm infants.Clinical epigenetics · 2020Article
- P2RX7 inhibitor suppresses exosome secretion and disease phenotype in P301S tau transgenic mice.Molecular neurodegeneration · 2020Article
- Alzheimer's disease risk geneeLife · 2020Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BIN1 is the most important risk locus for Late Onset Alzheimer's Disease (LOAD), after ApoE. BIN1 AD-associated SNPs correlate with Tau deposition as well as with brain atrophy. Furthermore, the level of neuronal-specific BIN1 isoform 1 protein is decreased in sporadic AD cases in parallel with neuronal loss, despite an overall increase in BIN1 total mRNA. To address the relationship between reduction of BIN1 and neuronal cell loss in the context of Tau pathology, we knocked-down endogenous murine Bin1 via stereotaxic injection of AAV-Bin1 shRNA in the hippocampus of mice expressing Tau P301S (PS19). We observed a statistically significant reduction in the number of neurons in the hippocampus of mice injected with AAV-Bin1 shRNA in comparison with mice injected with AAV control. To investigate whether neuronal loss is due to deletion of Bin1 selectively in neurons in presence Tau P301S, we bred Bin1flox/flox with Thy1-Cre and subsequently with PS19 mice. Mice lacking neuronal Bin1 and expressing Tau P301S showed increased mortality, without increased neuropathology, when compared to neuronal Bin1 and Tau P301S-expressing mice. The loss of Bin1 isoform 1 resulted in reduced excitability in primary neurons in vitro, reduced neuronal c-fos expression as well as in altered microglia transcriptome in vivo. Taken together, our data suggest that the contribution of genetic variation in BIN1 locus to AD risk could result from a cell-autonomous reduction of neuronal excitability due to Bin1 decrease, exacerbated by the presence of aggregated Tau, coupled with a non-cell autonomous microglia activation.
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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.