Platelet-derived secreted amyloid-precursor protein-β as a marker for diagnosing Alzheimer's disease.
A marker of Alzheimer's disease (AD) with a high sensitivity and specificity would facilitate a diagnosis at early stages. Blood platelets may be of particular interest in search of biomarkers, because they express amyloid-precursor protein (APP), and display a dysfunctional processing in AD. The aim of the present study is to establish and validate an assay for secreted amyloid-precursor protein (sAPP)-α and -β in platelets of AD and mild cognitively impaired (MCI) subjects, compared to healthy young and old controls. Freshly isolated platelet extracts (25 µg) were incubated with or without recombinant BACE1 (beta-site APP-Cleaving Enzyme; β-secretase, 8U) at 37°C and low pH and the levels of sAPP-α and sAPP-b were measured by specific ELISAs. Our data show that sAPP-α levels were not different between AD, MCI and control subjects. However, sAPP-β levels in MCI and AD were significantly elevated relative to controls. When recombinant BACE1 was added, no changes were seen in sAPP-α levels, but the processed sAPP-β levels were again markedly increased. The sAPP-β processing was specific and selective after 2.5 hours at 37°C, and was possibly mediated by exogenous BACE1, because it was blocked by a BACE1 inhibitor and BACE1 enzyme levels were enhanced in AD patients. Our data reveal that quantitive analysis of platelet sAPP-β assay by ELISA may be a novel diagnostic biomarker for MCI and AD.
Department of Psychiatry and Psychotherapy, Anichstr. 35, A-6020 Innsbruck, Austria. christian.humpel@i-med.ac.at.
Josef
J
Marksteiner
Christian
C
Humpel
D000368:Aged; D000544:Alzheimer Disease / Q000097:blood* / Q000175:diagnosis*; D016564:Amyloid beta-Protein Precursor / Q000032:analysis* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis*; D001792:Blood Platelets / Q000378:metabolism; D015153:Blotting, Western; D060825:Cognitive Dysfunction / Q000097:blood / Q000175:diagnosis; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers