Pancreatic β cell-secreted factor FGF23 attenuates Alzheimer's disease-related amyloid β-induced neuronal death.

Abstract

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline and memory impairment. The pathophysiology of AD may involve aggregated amyloid β (Aβ) accumulation, which may underlie the disease mechanism. Patients with diabetes exhibit an elevated risk of developing AD, indicating potential therapeutic implications upon elucidating the underlying mechanisms. We hypothesized that pancreatic β cell-secreted factors could protect neurons from Aβ-induced toxicity. Therefore, we established an experimental model to elucidate the communication between pancreatic β cells and neuronal cells. Notably, our findings demonstrate that pancreatic β cell culture supernatant effectively inhibits Aβ-induced neuronal cell death. Transcriptomic analysis showed significant up-regulation of multiple ribosomal protein genes in neuronal cells treated with pancreatic β cell culture supernatant. Fibroblast growth factor 23, a secreted factor from pancreatic β cells, significantly suppressed Aβ-induced neuronal cell death. Our findings suggest that pancreatic β cells may secrete previously unrecognized neuroprotective factors, thereby attenuating neuronal cell death in AD.