Impaired autophagy contributes to the build-up of Aβ plaques, hyperphosphorylated tau, and NFTs; mutations in presenilin-1 disrupt lysosomal acidification and Ca2+ homeostasis, impairing proteolysis; impaired mitophagy, mitochondrial damage, and oxidative stress are also linked to AD progression. Here, PSEN1 is linked to Alzheimer disease.