Epitopes described in "Aβ1-15/16 as a potential diagnostic marker in neurodegenerative diseases."

Article Authors:Magdalena Nutu; Philippe Bourgeois; Henrik Zetterberg; Erik Portelius; Ulf Andreasson; Stéphane Parent; Francesco Lipari; Sara Hall; Radu Constantinescu; Oskar Hansson; Kaj Blennow
Article Title:Aβ1-15/16 as a potential diagnostic marker in neurodegenerative diseases.
Reference Detail
Reference ID:1025621
Abstract:Cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) reflect brain biochemistry. Using combined immunoprecipitation and mass spectrometry, we have shown that amyloid beta 1-15 (A1-15) is produced by concerted - and -secretase cleavage of amyloid precursor protein (APP) and that the relative levels of A1-16 in AD compared to controls are increased. Furthermore, drug-induced -secretase inhibition enhances the relative levels of A1-15 and A1-16. Here, we investigate a novel immunoassay for A1-15/16 in a broad range of neurodegenerative conditions. The CSF level of A1-15/16 was measured by the bead-based amplified luminescent proximity homogeneous assay (Alpha technology). Concentrations of A1-15/16 were analyzed in subjects with Parkinson disease (PD; n = 90), PD with dementia (PDD) (n = 32), dementia with Lewy bodies (DLB) (n = 68), AD (n = 48), progressive supranuclear palsy (PSP) (n = 45), multiple system atrophy (MSA) (n = 46), and corticobasal degeneration (CBD) (n = 12). The detecting antibody is specific to the C-terminal epitope of A15. We found that a carboxypeptidase (CPB) present in fetal bovine serum (FBS), a component of the buffers used, degrades A1-16 to A1-15, which is then detected by the A1-15/16 assay. Significantly, lower levels of A1-15/16 were detected in PD, PDD, PSP, and MSA compared to other neurodegenerative diseases and controls. Using the specific A1-15/16 assay, a reliable quantification of A1-15 or A1-15/16 in CSF samples is obtained. We found reduced levels of A1-15 in parkinsonian disease groups. The molecular mechanism behind this reduction is at present unknown.
Reference Type:Literature
PubMed ID:23225274
Journal:Neuromolecular Med
Journal Volume:15
Article Pages:169-79
Journal ISSN:1535-1084
Article Chemical List:Amyloid beta-Peptides;Biological Markers;Epitopes;Peptide Fragments;Reagent Kits, Diagnostic;amyloid beta-protein (1-15);amyloid beta-protein (1-16);Carboxypeptidases
Article MeSH List:Aged; Aged, 80 and over; Amyloid beta-Peptides(cerebrospinal fluid); Animals; Antibody Specificity; Biological Markers; Biotinylation; Carboxypeptidases(metabolism); Cattle(blood; embryology); Diagnosis, Differential; Dose-Response Relationship, Immunologic; Epitopes(immunology); Female; Fetal Blood(enzymology); Humans; Immunoassay; Luminescent Measurements; Male; Middle Aged; Neurodegenerative Diseases(cerebrospinal fluid; diagnosis); Neuropsychological Tests; Peptide Fragments(cerebrospinal fluid); Reagent Kits, Diagnostic
Curation Last Updated:2014-10-03 22:52:28