From Proteinopathy to Immunopathy in Alzheimer's Disease—A Role for Astrocytic Calcineurin?

Abstract

The contemporary version of the most widely accepted model of Alzheimer's disease (AD), the β-amyloid cascade hypothesis, identifies β-amyloid oligomers as the primary neurotoxic species. Arising either from genetic mutations or environmental and lifestyle predisposing factors (collectively termed the ex-posome), β-amyloid oligomers gradually disrupt homeostatic cellular processes. At the cellular level, these alterations largely converge on two central pathobiological domains: proteinopa-thy (the disruption of cellular protein homeostasis) and immu-nopathy (the activation of immune-inflammatory pathways)