No abstract

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

Background/Aims: We have recently reported that platelet activity of the rate-limiting enzyme for β-amyloid peptide production is elevated in established Alzheimer’s disease. Laboratory investigation of the very early stages of dementia provides an opportunity to investigate pathological mechanisms before advanced disease hinders interpretation. Mild cognitive impairment (MCI) exists prior to obvious dementia, and is associated with increased risk of conversion to overt disease. Methods: We developed and used a fluorimetric assay to quantify platelet membrane β-secretase activity in 52 patients with MCI and 75 controls. Results: Platelet membrane β-secretase activity was 24% higher in individuals with MCI compared to controls (p = 0.001, unpaired t test with Welch correction). Conclusion: Elevated platelet β-secretase activity in subjects with MCI is an area for further study in relation to the etiology and diagnosis of MCI.

Several lines of evidence indicate that the Abeta 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 Abeta is generated by cleavage of the Met-Asp bond at position 671-672 of APP (amyloid precursor protein), catalysed by a proteolytic activity called beta-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 Abeta. 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.