Aβ1-15/16 as a Potential Diagnostic Marker in Neurodegenerative Diseases

Neuromolecular Med. 2013 Mar;15(1):169-79. doi: 10.1007/s12017-012-8208-8. Epub 2012 Dec 7.

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 (Aβ1-15) is produced by concerted β- and α-secretase cleavage of amyloid precursor protein (APP) and that the relative levels of Aβ1-16 in AD compared to controls are increased. Furthermore, drug-induced γ-secretase inhibition enhances the relative levels of Aβ1-15 and Aβ1-16. Here, we investigate a novel immunoassay for Aβ1-15/16 in a broad range of neurodegenerative conditions. The CSF level of Aβ1-15/16 was measured by the bead-based amplified luminescent proximity homogeneous assay (Alpha technology). Concentrations of Aβ1-15/16 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 Aβ15. We found that a carboxypeptidase (CPB) present in fetal bovine serum (FBS), a component of the buffers used, degrades Aβ1-16 to Aβ1-15, which is then detected by the Aβ1-15/16 assay. Significantly, lower levels of Aβ1-15/16 were detected in PD, PDD, PSP, and MSA compared to other neurodegenerative diseases and controls. Using the specific Aβ1-15/16 assay, a reliable quantification of Aβ1-15 or Aβ1-15/16 in CSF samples is obtained. We found reduced levels of Aβ1-15 in parkinsonian disease groups. The molecular mechanism behind this reduction is at present unknown.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Animals
  • Antibody Specificity
  • Biomarkers
  • Biotinylation
  • Carboxypeptidases / metabolism
  • Cattle / blood
  • Cattle / embryology
  • Diagnosis, Differential
  • Dose-Response Relationship, Immunologic
  • Epitopes / immunology
  • Female
  • Fetal Blood / enzymology
  • Humans
  • Immunoassay*
  • Luminescent Measurements
  • Male
  • Middle Aged
  • Neurodegenerative Diseases / cerebrospinal fluid*
  • Neurodegenerative Diseases / diagnosis
  • Neuropsychological Tests
  • Peptide Fragments / cerebrospinal fluid*
  • Reagent Kits, Diagnostic*

Substances

  • Amyloid beta-Peptides
  • Biomarkers
  • Epitopes
  • Peptide Fragments
  • Reagent Kits, Diagnostic
  • amyloid beta-protein (1-15)
  • amyloid beta-protein (1-16)
  • Carboxypeptidases