Title:Platelet-Derived Secreted Amyloid-Precursor Protein-β as a Marker for Diagnosing Alzheimer’s Disease
VOLUME: 10 ISSUE: 4
Author(s):Josef Marksteiner and Christian Humpel
Affiliation:Department of Psychiatry and Psychotherapy, Anichstr. 35, A-6020 Innsbruck, Austria.
Keywords:Alzheimer, Amyloid-precursor protein, APP, BACE1, Biomarker, ELISA, Diagnosis, Platelets.
Abstract: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.
