Calcium dysregulation could underlie lysosomal impairment in AD

Defective clearance of cellular waste by the lysosome, largely through autophagy, has been widely reported to contribute to the pathology of Alzheimer disease (AD). The underlying cause of autophagic or lysosomal impairment, however, remains poorly understood. New evidence from AD models published in Proceedings of the National Academy of Sciences indicates that aberrant calcium release from the endoplasmic reticulum (ER) leads to alkalization of the lysosome, which inhibits protease activity.