Aβ 4-42 could be one of the earliest and most prominent Aβ species deposited in AD brain. Sequencing of amyloid plaque cores showed that 64% of the isolated Aβ had a phenylalanine at its N-terminus, and indeed, IP/MS experiments identified Aβ 4-42 as a major Aβ species in AD patients. Additionally, Aβ 4-42 was found to be a component of cotton wool plaques in familial AD patients with the V261I PS1 mutation. Aβ 4-42 was discovered as well in amyloid deposits from vascular dementia and familial Danish dementia patients. These observations indicate that Aβ 4-42 may contribute to the development of multiple CNS diseases.