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Background
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Accumulation of the amyloid-β, peptide (Aβ,) in the cerebral cortex is a critical event in the pathogenesis of Alzheimers disease. The β,amyloid protein precursor (APP) is cleaved by one of two β,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? β,secretase to generate the 4 kDa amyloid-β, peptide (Aβ,), which is deposited in the Alzheimers disease patients brains. BACE was identified by several groups independently and designated β,-site APP cleaving enzyme (BACE) . BACE is a transmembrane aspartic protease and co-localizes with APP. BACE2 also cleaves APP at β,-site and at a different site within Aβ,. BACE2 locates on chromosome 21q22.3, the so-called Down critical region, suggesting that BACE2 and Aβ, may also contribute to the pathogenesis of Down syndrome.
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