For example, pathogenic variants in APP [precursor to amyloid-β (Aβ) peptide] and PSEN1/PSEN2 (subunit of the protease that generates Aβ peptide) lead to the over-production and/or altered production of Aβ peptide, resulting in most instances in an early-onset AD clinical phenotype and the presence of AD neuropathologic change in the brain consisting of Aβ plaques and tau-positive NFTs. The gene discussed is PSEN1; the disease is Alzheimer disease.