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Evaluating Amyloid-beta Oligomers in Cerebrospinal Fluid as a Biomarker for Alzheimer's Disease

Holtta, Mikko; Hansson, Oskar LU ; Andreasson, Ulf; Hertze, Joakim LU ; Minthon, Lennart LU ; Nägga, Katarina LU ; Andreasen, Niels; Zetterberg, Henrik and Blennow, Kaj (2013) In PLoS ONE 8(6).
Abstract
The current study evaluated amyloid-beta oligomers (A beta o) in cerebrospinal fluid as a clinical biomarker for Alzheimer's disease (AD). We developed a highly sensitive A beta o ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized A beta with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic A beta o levels. Three clinical materials of well characterized AD patients (n = 199) and cognitively healthy controls (n = 148) from different clinical centers were included, together with a clinical material of... (More)
The current study evaluated amyloid-beta oligomers (A beta o) in cerebrospinal fluid as a clinical biomarker for Alzheimer's disease (AD). We developed a highly sensitive A beta o ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized A beta with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic A beta o levels. Three clinical materials of well characterized AD patients (n = 199) and cognitively healthy controls (n = 148) from different clinical centers were included, together with a clinical material of patients with MCI (n = 165). A beta o levels were elevated in the all three AD-control comparisons although with a large overlap and a separation from controls that was far from complete. Patients with MCI who later converted to AD had increased A beta o levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable A beta o levels in CSF is clearly associated with AD, but the overlap is too large for the test to have any diagnostic potential on its own. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
8
issue
6
publisher
Public Library of Science
external identifiers
  • wos:000320363300078
  • scopus:84879149021
ISSN
1932-6203
DOI
10.1371/journal.pone.0066381
language
English
LU publication?
yes
id
2a6855ac-7076-4538-8199-497af777db2f (old id 3987368)
date added to LUP
2013-09-02 10:41:30
date last changed
2019-02-20 05:27:48
@article{2a6855ac-7076-4538-8199-497af777db2f,
  abstract     = {The current study evaluated amyloid-beta oligomers (A beta o) in cerebrospinal fluid as a clinical biomarker for Alzheimer's disease (AD). We developed a highly sensitive A beta o ELISA using the same N-terminal monoclonal antibody (82E1) for capture and detection. CSF samples from patients with AD, mild cognitive impairment (MCI), and healthy controls were examined. The assay was specific for oligomerized A beta with a lower limit of quantification of 200 fg/ml, and the assay signal showed a tight correlation with synthetic A beta o levels. Three clinical materials of well characterized AD patients (n = 199) and cognitively healthy controls (n = 148) from different clinical centers were included, together with a clinical material of patients with MCI (n = 165). A beta o levels were elevated in the all three AD-control comparisons although with a large overlap and a separation from controls that was far from complete. Patients with MCI who later converted to AD had increased A beta o levels on a group level but several samples had undetectable levels. These results indicate that presence of high or measurable A beta o levels in CSF is clearly associated with AD, but the overlap is too large for the test to have any diagnostic potential on its own.},
  articleno    = {e66381},
  author       = {Holtta, Mikko and Hansson, Oskar and Andreasson, Ulf and Hertze, Joakim and Minthon, Lennart and Nägga, Katarina and Andreasen, Niels and Zetterberg, Henrik and Blennow, Kaj},
  issn         = {1932-6203},
  language     = {eng},
  number       = {6},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Evaluating Amyloid-beta Oligomers in Cerebrospinal Fluid as a Biomarker for Alzheimer's Disease},
  url          = {http://dx.doi.org/10.1371/journal.pone.0066381},
  volume       = {8},
  year         = {2013},
}