Josef Marksteiner and Christian Humpel Pages 297 - 303 ( 7 )
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.
Alzheimer, Amyloid-precursor protein, APP, BACE1, Biomarker, ELISA, Diagnosis, Platelets.
Department of Psychiatry and Psychotherapy, Anichstr. 35, A-6020 Innsbruck, Austria.