Expression and activity of β-site amyloid precursor protein cleaving enzyme in Alzheimer's disease

Several lines of evidence indicate that the A beta peptide is involved at some level in the pathological process that results in the clinical symptoms of AD (Alzheimer's disease). The N-terminus of A beta is generated by cleavage of the Met-Asp bond at position 671-672 of APP (amyloid precursor protein), catalysed by a proteolytic activity called P-secretase. Two 'beta-secretase' proteases have been identified: BACE (beta-site APP-cleaving enzyme) and BACE2. The cause of sporadic AD is currently unknown, but some studies have reported elevated BACE/beta-secretase activity in brain regions affected by the disease. We have demonstrated that robust beta-secretase activity is also detectable in platelets that contain APP and release A beta. This review considers the current evidence for alterations in beta-secretase activity, and/or alterations in BACE expression, in post-mortem brain tissue and platelets from individuals with AD.