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ALZHEIMER’S DISEASE RISK FACTOR BIN1: LINKING MICROGLIAL DEFICIENCY TO NEUROINFLAMMATION AND REGULATION OF ADULT HIPPOCAMPAL NEUROGENESIS
Irini Thanouand 9 co-authors
Hellenic Institute Pasteur
FENS Forum 2026 (2026)
Barcelona, Spain
Board PS07-10AM-191
Presentation
Date TBA
Board: PS07-10AM-191
Event Information
Poster Board
PS07-10AM-191
Poster
View posterAbstract
Bridging Integrator 1 (BIN1) has been identified as the second major genetic risk factor for Late-Onset Alzheimer’s Disease (LOAD). Although BIN1 has been extensively studied in neuronal contexts, its function in microglia remains underexplored. Given the pivotal role of microglia in neuroinflammation and adult hippocampal neurogenesis (AHN), both central to Alzheimer’s disease pathology, investigating BIN1 in this context may yield critical insights into disease mechanisms.
To this end, we employed a conditional double transgenic mouse model with microglia-specific BIN1 knockout. Our findings reveal that BIN1 deficiency reshapes microglial molecular and phenotypic profiles in a region-specific manner. Following LPS-induced inflammation, BIN1 deletion in both cortex and hippocampus enhanced type I interferon signaling and induced a hyper-ramified, intermediate activation state. However, cortical microglia displayed a pronounced pro-inflammatory phenotype, characterized by increased cytokine and chemokine expression, expansion of proliferative and CD11c⁺ subsets, and elevated CD68 levels. In contrast, hippocampal microglia adopted a more immunomodulatory profile, with reduced pro-inflammatory cytokines, increased neuroprotective mediators, and decreased CD68 expression, indicative of lower phagocytic activity. Notably, under homeostatic conditions, BIN1 deletion expanded neural stem cells and progenitor populations in the subgranular zone, revealing a novel role for microglial BIN1 in regulating AHN through non-cell-autonomous mechanisms. Preliminary data indicate that conditioned media from BIN1 siRNA-transfected BV2 cells promote survival and proliferation in adult hippocampal neural stem cells.
To this end, we employed a conditional double transgenic mouse model with microglia-specific BIN1 knockout. Our findings reveal that BIN1 deficiency reshapes microglial molecular and phenotypic profiles in a region-specific manner. Following LPS-induced inflammation, BIN1 deletion in both cortex and hippocampus enhanced type I interferon signaling and induced a hyper-ramified, intermediate activation state. However, cortical microglia displayed a pronounced pro-inflammatory phenotype, characterized by increased cytokine and chemokine expression, expansion of proliferative and CD11c⁺ subsets, and elevated CD68 levels. In contrast, hippocampal microglia adopted a more immunomodulatory profile, with reduced pro-inflammatory cytokines, increased neuroprotective mediators, and decreased CD68 expression, indicative of lower phagocytic activity. Notably, under homeostatic conditions, BIN1 deletion expanded neural stem cells and progenitor populations in the subgranular zone, revealing a novel role for microglial BIN1 in regulating AHN through non-cell-autonomous mechanisms. Preliminary data indicate that conditioned media from BIN1 siRNA-transfected BV2 cells promote survival and proliferation in adult hippocampal neural stem cells.
Together, these findings identify BIN1 as a key regulator of microglial activation and highlight region-specific responses, guiding future studies aimed at elucidating the non–cell-autonomous effects of microglial BIN1.
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