NeuroMolecular Medicine

, Volume 15, Issue 1, pp 169–179

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

  • Magdalena Nutu
  • Philippe Bourgeois
  • Henrik Zetterberg
  • Erik Portelius
  • Ulf Andreasson
  • Stéphane Parent
  • Francesco Lipari
  • Sara Hall
  • Radu Constantinescu
  • Oskar Hansson
  • Kaj Blennow
Original Paper

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.

Keywords

Aβ AlphaLISA Amyloid PD AD 

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Magdalena Nutu
    • 1
  • Philippe Bourgeois
    • 2
  • Henrik Zetterberg
    • 1
  • Erik Portelius
    • 1
  • Ulf Andreasson
    • 1
  • Stéphane Parent
    • 2
  • Francesco Lipari
    • 2
  • Sara Hall
    • 3
    • 4
  • Radu Constantinescu
    • 5
  • Oskar Hansson
    • 1
    • 3
    • 4
  • Kaj Blennow
    • 1
  1. 1.Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska AcademyUniversity of Gothenburg, Sahlgrenska University Hospital/MölndalMölndalSweden
  2. 2.PerkinElmer Biosignal, Inc.MontrealCanada
  3. 3.Department of Clinical SciencesLund UniversityLundSweden
  4. 4.Department of NeurologySkåne University HospitalLundSweden
  5. 5.Neurology ClinicSahlgrenka University HospitalGöteborgSweden

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