Examining an endogenous modulator of chaperone‐mediated autophagy in neurons across Braak stages of Alzheimer's disease

Defective clearance of tau by neuronal autophagy has been implicated in the accumulation of toxic forms of tau in Alzheimer’s disease (AD). A novel, endogenous activator of chaperone‐mediated autophagy (CMA‐modulator) was identified in cell culture experiments (Cuervo laboratory, unpublished data). It is unclear what role this endogenous CMA‐modulator plays in AD. We hypothesized that loss of the CMA‐modulator in neurons could lead to decreased clearance of abnormal tau monomers, promoting the accumulation of toxic forms of tau. This study examined the proportion of neurons with CMA‐modulator in postmortem brain tissue from subjects with a range of AD neuropathologic changes as well as both amnestic and non‐amnestic AD presentation.