APP and Alzheimer disease: Individuals with DS will develop AD pathology by their mid-30’s-40’s, including cortical thinning, brain atrophy, amyloid-beta peptide (Aβ) containing senile plaques followed by tau-positive neurofibrillary tangles (NFTs) [30, 48, 68, 98], with reports of amyloid deposition in individuals as early as their teens [59, 96].