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A beta 1-15/16 as a Potential Diagnostic Marker in Neurodegenerative Diseases

Nutu, Magdalena; Bourgeois, Philippe; Zetterberg, Henrik; Portelius, Erik; Andreasson, Ulf; Parent, Stephane; Lipari, Francesco; Hall, Sara LU ; Constantinescu, Radu and Hansson, Oskar, et al. (2013) In NeuroMolecular Medicine 15(1). p.169-179
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 (A beta 1-15) is produced by concerted beta- and alpha-secretase cleavage of amyloid precursor protein (APP) and that the relative levels of A beta 1-16 in AD compared to controls are increased. Furthermore, drug-induced gamma-secretase inhibition enhances the relative levels of A beta 1-15 and A beta 1-16. Here, we investigate a novel immunoassay for A beta 1-15/16 in a broad range of neurodegenerative conditions. The CSF level of A beta 1-15/16 was measured by the bead-based amplified luminescent proximity homogeneous assay (Alpha technology).... (More)
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 (A beta 1-15) is produced by concerted beta- and alpha-secretase cleavage of amyloid precursor protein (APP) and that the relative levels of A beta 1-16 in AD compared to controls are increased. Furthermore, drug-induced gamma-secretase inhibition enhances the relative levels of A beta 1-15 and A beta 1-16. Here, we investigate a novel immunoassay for A beta 1-15/16 in a broad range of neurodegenerative conditions. The CSF level of A beta 1-15/16 was measured by the bead-based amplified luminescent proximity homogeneous assay (Alpha technology). Concentrations of A beta 1-15/16 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 A beta 15. We found that a carboxypeptidase (CPB) present in fetal bovine serum (FBS), a component of the buffers used, degrades A beta 1-16 to A beta 1-15, which is then detected by the A beta 1-15/16 assay. Significantly, lower levels of A beta 1-15/16 were detected in PD, PDD, PSP, and MSA compared to other neurodegenerative diseases and controls. Using the specific A beta 1-15/16 assay, a reliable quantification of A beta 1-15 or A beta 1-15/16 in CSF samples is obtained. We found reduced levels of A beta 1-15 in parkinsonian disease groups. The molecular mechanism behind this reduction is at present unknown. (Less)
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organization
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Contribution to journal
publication status
published
subject
keywords
A beta, AlphaLISA, Amyloid, PD, AD
in
NeuroMolecular Medicine
volume
15
issue
1
pages
169 - 179
publisher
Humana Press
external identifiers
  • wos:000315631000014
  • scopus:84874678235
ISSN
1535-1084
DOI
10.1007/s12017-012-8208-8
language
English
LU publication?
yes
id
a6414be0-c0da-4c7f-835f-6f10d4642972 (old id 3670201)
date added to LUP
2013-05-02 09:00:45
date last changed
2019-02-20 02:03:35
@article{a6414be0-c0da-4c7f-835f-6f10d4642972,
  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 (A beta 1-15) is produced by concerted beta- and alpha-secretase cleavage of amyloid precursor protein (APP) and that the relative levels of A beta 1-16 in AD compared to controls are increased. Furthermore, drug-induced gamma-secretase inhibition enhances the relative levels of A beta 1-15 and A beta 1-16. Here, we investigate a novel immunoassay for A beta 1-15/16 in a broad range of neurodegenerative conditions. The CSF level of A beta 1-15/16 was measured by the bead-based amplified luminescent proximity homogeneous assay (Alpha technology). Concentrations of A beta 1-15/16 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 A beta 15. We found that a carboxypeptidase (CPB) present in fetal bovine serum (FBS), a component of the buffers used, degrades A beta 1-16 to A beta 1-15, which is then detected by the A beta 1-15/16 assay. Significantly, lower levels of A beta 1-15/16 were detected in PD, PDD, PSP, and MSA compared to other neurodegenerative diseases and controls. Using the specific A beta 1-15/16 assay, a reliable quantification of A beta 1-15 or A beta 1-15/16 in CSF samples is obtained. We found reduced levels of A beta 1-15 in parkinsonian disease groups. The molecular mechanism behind this reduction is at present unknown.},
  author       = {Nutu, Magdalena and Bourgeois, Philippe and Zetterberg, Henrik and Portelius, Erik and Andreasson, Ulf and Parent, Stephane and Lipari, Francesco and Hall, Sara and Constantinescu, Radu and Hansson, Oskar and Blennow, Kaj},
  issn         = {1535-1084},
  keyword      = {A beta,AlphaLISA,Amyloid,PD,AD},
  language     = {eng},
  number       = {1},
  pages        = {169--179},
  publisher    = {Humana Press},
  series       = {NeuroMolecular Medicine},
  title        = {A beta 1-15/16 as a Potential Diagnostic Marker in Neurodegenerative Diseases},
  url          = {http://dx.doi.org/10.1007/s12017-012-8208-8},
  volume       = {15},
  year         = {2013},
}