Platelet β-secretase activity is increased in Alzheimer's disease

P-Secretase activity is the rate-limiting step in A beta peptide production from amyloid precursor protein. A beta is a major component of Alzheimer's disease (AD) cortical amyloid plaques. P-Secretase activity is elevated in post mortem brain tissue in AD. The current study investigated whether P-secretase activity was also elevated in peripheral blood platelets. We developed a novel fluorimetric P-secretase activity assay to investigate platelets isolated from individuals with AD (n = 86), and age-matched controls (n = 115). Platelet membrane P-secretase activity (expressed as initial rate) varied over fourfold between individuals, raising important questions about in vivo regulation of this proteolytic activity. Nonetheless, we identified a significant 17% increase in platelet membrane P-secretase activity in individuals with AD compared to controls (p = 0.0003, unpaired t-test). Platelet membrane P-secretase activity did not correlate with mini-mental state examination (MMSE) score in the AD group (mean MMSE= 17.7, range 1-23), indicating that the increase did not occur as a secondary result of the disease process, and may even have preceded symptom onset. (D 2006 Elsevier Inc. All rights reserved.