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Background
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Accumulation of the amyloid-?2, peptide (A?2,) in the cerebral cortex is a critical event in the pathogenesis of Alzheimers disease. The ?2,amyloid protein precursor (APP) is cleaved by one of two ?2,secretases (BACE and BACE2), producing a soluble derivative of the protein and a membrane anchored 99-amino acid carboxy-terminal fragment (C99). The C99 fragment serves as substrate for? ?2,secretase to generate the 4 kDa amyloid-?2, peptide (A?2,), which is deposited in the Alzheimers disease patients brains. BACE was identified by several groups independently and designated ?2,-site APP cleaving enzyme (BACE) . BACE is a transmembrane aspartic protease and co-localizes with APP. BACE2 also cleaves APP at ?2,-site and at a different site within A?2,. BACE2 locates on chromosome 21q22.3, the so-called Down critical region, suggesting that BACE2 and A?2, may also contribute to the pathogenesis of Down syndrome.
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