PSEN2 and Down syndrome: On the other hand, over 68 mutations in APP, 300 in Presenilin 1 (PSEN1), and 64 in Presenilin 2 (PSEN2) (www.alzforum.org/mutations), as well as the triplication of chromosome 21 (Down syndrome), which bears the APP gene, often results in increased production of longer forms of the amyloid beta (Aβ) peptides that are more prone to oligomerization, leading to an early onset of AD.