RAG Files/Alzheimer's Disease - Causes - 4.txt

Early onset
Only 1–2% of Alzheimer's cases are inherited due to autosomal dominant effects, as Alzheimer's is highly polygenic. When the disease is caused by autosomal dominant variants, it is known as early onset familial Alzheimer's disease, which is rarer and has a faster rate of progression.[13] Less than 5% of sporadic Alzheimer's disease have an earlier onset,[13] and early-onset Alzheimer's is about 90% heritable.[48][49] FAD usually implies multiple persons affected in one or more generation.[medical citation needed][57]

Early onset familial Alzheimer's disease can be attributed to mutations in one of three genes: those encoding amyloid-beta precursor protein (APP) and presenilins PSEN1 and PSEN2.[31] Most mutations in the APP and presenilin genes increase the production of a small protein called amyloid beta (Aβ)42, which is the main component of amyloid plaques.[58] Some of the mutations merely alter the ratio between Aβ42 and the other major forms—particularly Aβ40—without increasing Aβ42 levels in the brain.[59] Two other genes associated with autosomal dominant Alzheimer's disease are ABCA7 and SORL1.[60]