Alzheimer's Disease Research - Diagnosis, Memory Loss, Heredity, Treatment, Medication

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Platelet beta-secretase activity is increased in Alzheimer's disease.

Johnston JA, Liu WW, Coulson DT, Todd S, Murphy S, Brennan S, Foy CJ, Craig D, Irvine GB, Passmore AP

Queen's University Belfast, School of Medicine and Dentistry, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, United Kingdom. j.a.johnston@qub.ac.uk

beta-Secretase activity is the rate-limiting step in Abeta peptide production from amyloid precursor protein. Abeta is a major component of Alzheimer's disease (AD) cortical amyloid plaques. beta-Secretase activity is elevated in post mortem brain tissue in AD. The current study investigated whether beta-secretase activity was also elevated in peripheral blood platelets. We developed a novel fluorimetric beta-secretase activity assay to investigate platelets isolated from individuals with AD (n=86), and age-matched controls (n=115). Platelet membrane beta-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 beta-secretase activity in individuals with AD compared to controls (p=0.0003, unpaired t-test). Platelet membrane beta-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.

Published 28 March 2008 in Neurobiol Aging, 29(5): 661-8.
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