Amyloid-β Impairs Vesicular Secretion in Neuronal and Astrocyte Peptidergic Transmission.

摘要: Regulated secretion of neuropeptides and neurotrophic factors critically modulates function plasticity synapses circuitries. It is believed that rising amyloid-beta (Aβ) concentrations, synaptic dysfunction network disorganization underlie early phases Alzheimer’s disease (AD). Here, we analyze the impact soluble Aβ1-42 assemblies on peptidergic in cortical neurons astrocytes. We show astrocytes differentially produce release carboxypeptidase E (CPE) secretogranin III (SgIII), two dense-core vesicle (DCV) markers belonging to regulated secretory pathway. Importantly, Aβ1-42, but not scrambled dramatically impairs basal Ca2+-regulated secretions endogenously produced CPE SgIII cultured Additionally, KCl-evoked DCV cargo BDNF lowered by administration, whereas glutamate from vesicles remains unchanged. In agreement with cell culture results, effects are faithfully recapitulated acute adult brain slices. These results demonstrate neuronal astrocyte cargos impaired Aβ vitro situ. Furthermore, Aβ-induced dysregulated transmission could have an important role pathogenesis AD possible candidates as cerebrospinal fluid biomarkers.