CSTB and Alzheimer disease: In addition to the defects of autophagy at the early stages, autolysosomal proteolysis is significantly impaired in AD and its defect is one of the key pathogenic factors in AD (98, 99); thus, selectively enhancing lysosomal activity by genetic ablation of cystatin B to enhance the clearance of autophagic substrates and ameliorate amyloid pathology and memory deficits in TgCRND8 AD mouse models (100).