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The APP gene encodes amyloid precursor protein, a transmembrane protein whose proteolysis gives rise to Aβ peptides. Mutations in APP are associated with Alzheimer's disease and Cerebral Amyloid Angiopathy.
PSEN1 encodes presenilin-1, a subunit of γ-secretase, the aspartyl protease responsible for Aβ generation. Over 180 mutations in PSEN1 have been reported and mutations in PSEN1 are the most common cause of early onset Alzheimer's disease.
The gene PSEN2 encodes presenilin-2, a subunit of γ-secretase, the aspartyl protease responsible for Aβ generation. Missense mutations in PSEN2 are a rare cause of early onset Alzheimer's disease.
MAPT encodes the microtubule associated protein tau, a protein central to Alzheimer’s disease neuropathology. MAPT mutations are not linked to familial forms of AD, but can cause frontotemporal dementia (FTD) and several other tauopathies. The pathogenic mutations, which can be either exonic or intronic, generally alter the relative production of tau isoforms and lead to changes in microtubule assembly and/or the propensity of tau to aggregate.
Selected Recent Reviews:
Early-onset familial Alzheimer's disease (EOFAD) (Wu et al., 2012)
Familial Alzheimer's disease sustained by presenilin 2 mutations: Systematic review of literature and genotype-phenotype correlation (Canevelli et al., 2014)
Systematic review and meta-analysis of Japanese familial Alzheimer's disease and FTDP-17 (Kasuga et al., 2015)
Frontotemporal dementia caused by microtubule-associated protein tau gene (MAPT) mutations (Ghetti et al., 2015)