APP and Alzheimer disease: Key characteristics of AD are aggregation of amyloid-β plaques, neurofibrillary tangles, neuroinflammation, and BBB breakdown.46 Amyloid-β is naturally produced in the brain, first as amyloid precursor protein (APP).55 In a healthy brain, presenilin proteins (PSEN), presenilin-1, and presenilin-2, cleave APP most often into amyloid-β40 (~90%).55,56 Commonly in familial AD, mutations in APP or in PSEN cause cleavage of APP into amyloid-β42.