A Neuron-Glial Model of Exosomal Release in the Onset and Progression of Alzheimer's Disease

Exosomes are nano-sized extracellular vesicles that perform a variety of biological functions linked to the pathogenesis of various neurodegenerative disorders. In Alzheimer's disease (AD), for examples, exosomes are responsible for the release of Aβ oligomers, and their extracellular accumulation, although the underpinning molecular machinery remains elusive. We propose a novel model for Alzheimer's Aβ accumulation based on Ca ²⁺-dependent exosome release from astrocytes. Moreover, we exploit our model to assess how temperature dependence of exosome release could interact with Aβ neurotoxicity. We predict that voltage-gated Ca ²⁺ channels (VGCCs) along with the transient-receptor potential M8 (TRPM8) channel are crucial molecular components in Alzheimer's progression.