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

被引：64

作者：

Johnston, J. A. ^{[1
]}

Liu, W. W. ^{[1
]}

Coulson, D. T. R. ^{[1
]}

Todd, S. ^{[1
]}

Murphy, S. ^{[1
]}

Brennan, S. ^{[1
]}

Foy, C. J. ^{[1
]}

Craig, D. ^{[1
]}

Irvine, G. B. ^{[1
]}

Passmore, A. P. ^{[1
]}

机构：

[1] Queens Univ Belfast, Div Psychiat & Neurosci, Sch Med & Dent, Belfast BT9 7BL, Antrim, North Ireland

来源：

NEUROBIOLOGY OF AGING | 2008年 / 29卷 / 05期

关键词：

A beta; amyloid precursor protein; biomarker; blood; neurodegeneration; protease;

D O I：

10.1016/j.neurobiolaging.2006.11.003

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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.

引用

页码：661 / 668

页数：8

共 37 条

[1] Platelet APP isoform ratios correlate with declining cognition in AD [J].