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

Holtta, Mikko ; Hansson, Oskar LU orcid ; 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
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
8
issue
6
article number
e66381
publisher
Public Library of Science (PLoS)
external identifiers
  • wos:000320363300078
  • scopus:84879149021
  • pmid:23799095
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
2016-04-01 13:22:18
date last changed
2022-05-15 04:50:50
@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.}},
  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 (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{Evaluating Amyloid-beta Oligomers in Cerebrospinal Fluid as a Biomarker for Alzheimer's Disease}},
  url          = {{https://lup.lub.lu.se/search/files/3331726/4362372.pdf}},
  doi          = {{10.1371/journal.pone.0066381}},
  volume       = {{8}},
  year         = {{2013}},
}