HSPA5 and Alzheimer disease: Importantly, the extracellular chaperone α2-M, a ligand of GRP78 at the plasma membrane, is co-localized with plaques in AD (Yerbury and Wilson, 2010), and it has been shown both to protect cells from Aβ toxicity and to favor Aβ removal from the brain (reviewed in Yerbury and Wilson, 2010).