Previous studies have shown that mutations in PS1 cause lysosome impairment,66 EVs contain lysosomal proteins,70 and EV marker proteins such as Alix and flotillin-1 are present in AD amyloid plaques.14,20 We found that inhibition of autophagy (by exposure to bafilomycin A or CRISPR-Cas9-mediated knockdown of cathepsin D) in cells expressing mutant PS1 resulted in increased release of EVs with elevated amounts of Aβ42, suggesting that impaired autophagy may result in the release of pathogenic EVs in AD. Here, PDCD6IP is linked to Alzheimer disease.