PSEN2, on chromosome 1, is another risk-factor gene for AD, especially EOAD among a very small European population. The most well-known group with dementia from PSEN2 mutation is families with Volga German ancestry. AD arising from PSEN2 mutations can be highly variable, and may occur between the ages of 40 and 75 years.5,21,22 The first PSEN2 mutation in AD patients was described in 1995.5,23–25 Patients with PSEN2 mutation have not been reported in Korea, the People’s Republic of China, or Japan, but silent mutations have been detected in Japan.26 A few PSEN2 mutations, such as Leu143His or Arg143His, have not been associated with any neurodegenerative phenotype.27 Two PSEN2 mutations, Arg62His and Arg71Trp, may be involved in breast cancer, although the pathomechanism is not clear.28 Table 1 summarizes all mutations described in APP, PSEN1, and PSEN2 genes that may be involved in AD progression.
