The APP gene is located on chromosome 21. Triplication of chromosome 21 results in the triplication of the APP gene, which might enhance APP expression and Abeta accumulation. Down syndrome patients have been reported to develop AD pathology (deposition of senile plaques and neurofibrillary tangles) earlier than those without Down syndrome.11 These findings suggest that overexpression of APP might be related to AD pathology. The APP gene contains 19 exons for encoding the APP protein. The Abeta peptide is encoded by exons 16 and 17. Following transcription and alternative splicing, at least five isoforms of APP protein were identified, which contain the Abeta peptide sequence.12 However, APP seems to be a very rare risk factor for AD, as 21 and three mutations were described at exon 17 and 16, respectively. Most of the pathogenic APP mutations were located near the cleavage sites of alpha, beta, and gamma secretase enzymes, which suggests they might be involved in the onset of AD through altering the proteolysis of the Abeta peptide.13,14 N-terminal mutations in the Abeta sequence can affect the endosomal/lysosomal cleavage of
