Platelet beta-secretase activity is increased in Alzheimer's disease.
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.
Johnston
J A
JA
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
Liu
W W
WW
Coulson
D T R
DT
Todd
S
S
Murphy
S
S
Brennan
S
S
Foy
C J
CJ
Craig
D
D
Irvine
G B
GB
Passmore
A P
AP
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases / Q000097:blood*; D001792:Blood Platelets / Q000201:enzymology*; D004789:Enzyme Activation; D005260:Female; D006801:Humans; D008297:Male
D053829:Amyloid Precursor Protein Secretases