title: Expression and activity of beta-site amyloid precursor protein cleaving enzyme in Alzheimer's disease.
abstract: 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.
authors.affiliation: 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
authors.forename: J A
authors.initials: JA
authors.lastname: Johnston
authors.forename: W W
authors.initials: WW
authors.lastname: Liu
authors.forename: S A
authors.initials: SA
authors.lastname: Todd
authors.forename: D T R
authors.initials: DT
authors.lastname: Coulson
authors.forename: S
authors.initials: S
authors.lastname: Murphy
authors.forename: G B
authors.initials: GB
authors.lastname: Irvine
authors.forename: A P
authors.initials: AP
authors.lastname: Passmore
mesh_terms: 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
chemical_list: 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