APP and early-onset autosomal dominant Alzheimer disease: Alzheimer’s disease (AD) is the most common neurodegenerative disease, which sporadically affects people above age 65.5,6 Pathophysiologically, an altered proteostasis with the accumulation of misfolded amyloid beta (Abeta) and phosphorylated tau (pTau) proteins mediate neuronal loss and cognitive decline.7,8 Neuropathologically, AD is characterized by the combination of pTau-positive neurofibrillary tangles (NFTs) and Abeta-positive plaques and occasional vascular deposits.