Expression and activity of beta-site amyloid precursor protein cleaving enzyme in Alzheimer's disease.
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.
Johnston
J A
JA
School of Biology and Biochemistry, The Queen's University of Belfast, Medical Biology Centre, Belfast BT9 7BL, Northern Ireland. j.a.johnston@qub.ac.uk
Liu
W W
WW
Todd
S A
SA
Coulson
D T R
DT
Murphy
S
S
Irvine
G B
GB
Passmore
A P
AP
D000544:Alzheimer Disease / Q000097:blood / Q000201:enzymology*; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism; D001921:Brain / Q000201:enzymology / Q000378:metabolism; D002784:Cholesterol / Q000009:adverse effects; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans
D016564:Amyloid beta-Protein Precursor; D002784:Cholesterol; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human