Accumulation of the amyloid- (A ) plaque in the cerebral cortex is a critical event in the pathogenesis of AlzheimerÕs disease. A peptide is generated by proteolytic cleavage of the amyloid protein precursor (APP) at - and -sites by proteases. The long-sought secretase was recently identified by several groups independently and designated beta-site APP cleaving enzyme (BACE) and aspartyl protease 2 (Asp2)1-4. A BACE homolog was recently cloned and designated BACE2, Asp1, DRAP (for Down region aspartic protease), and memapsin 14-9. BACE2 also cleaves APP at -site and at a different site within A 8. BACE2 locates on chromosome 21q22.3, the so-called ÔDown critical regionÕ, suggesting that BACE2 and A may also contribute to the pathogenesis of Down syndrome6,7
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