Neurotrophic signaling deficiency exacerbates environmental risks for Alzheimer’s disease pathogenesis
Zhourui Wu, Chun Chen, Seong Su Kang, Xia Liu, Xiaohuan Gu, Shan Ping Yu, C. Dirk Keene, Liming Cheng, Keqiang Ye
Abstract
Significance The molecular mechanisms accounting for the environmental risk factor stimulation of Alzheimer’s disease (AD) pathogenesis including traumatic brain injury, diabetes, and chronic cerebral hypoperfusion remain unclear. The BDNF/TrkB signaling pathway plays a critical role in neuronal synaptic plasticity and neuronal survival. Since the BDNF/TrkB pathway is reduced during aging and in AD human brains, we hypothesize that the crosstalk between these risk factors and BDNF/TrkB deficiency may mediate AD pathologies. Our previous studies establish that the C/EBPβ/δ-secretase pathway plays a pivotal role in triggering the major AD pathologies. Therefore, in the current report, we provide extensive evidence demonstrating that BDNF/TrkB reduction regulates this pathway activation under various risk factors, mediating Aβ and Tau pathology spreading in the brain.