FGFR1 agonists alleviate pathology and cognitive impairment in an Alzheimer's disease mouse model

Alzheimer's disease (AD) is the leading cause of dementia, characterized by the buildup of amyloid plaques and neurofibrillary tangles, which lead to neuronal damage and trigger inflammatory responses in glial cells. The fibroblast growth factor receptor 1 (FGFR1)-mediated signaling pathways support the function of damaged neurons and modulate the inflammatory response. The FGFR1 agonists, including Fibroblast growth factor 1 (FGF1) and FG loop peptide (FGL), have been implicated in multiple disease therapies. However, whether FGFR1 agonists can improve pathology and cognitive function in AD remains unknown. This study showed that administration of FGF1 and FGL to the AD mouse model reversed spatial memory impairment, enhanced neurogenesis, suppressed reactive astrogliosis, and restricted dystrophic neurites. However, only FGF1 treatment reduced the deposition of senile plaque. In microglial culture studies, FGF1 improves the phagocytosis ability of microglia, but this effect is blocked by the FGFR1-specific inhibitor. Together, our findings suggested that FGFR1 agonists alleviate pathological and cognitive impairments in the AD mouse model.