APP and Down syndrome: This hypothesis initiated with the presence of Aβ plaques in the brain of many AD patients, and gained strength and momentum as carriers with genetic mutations in APP and presenilin (PSEN) were found to have increased Aβ production and develop autosomal dominant AD, and individuals with Down’s syndrome have three copies of APP, develop Aβ plaques and many develop dementia (Kolata, 1985; Selkoe and Hardy, 2016).