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Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: Diagnostic Performance in a Homogeneous Mono-Center Population

Johansson, Per LU ; Mattsson, Niklas; Hansson, Oskar LU ; Wallin, Anders; Johansson, Jan-Ove; Andreasson, Ulf; Zetterberg, Henrik; Blennow, Kaj LU and Svensson, Johan (2011) In Journal of Alzheimer's Disease 24(3). p.537-546
Abstract
The cerebrospinal fluid (CSF) biomarkers amyloid-beta (A beta)(1-42), T-tau, and P-tau have good diagnostic accuracy for clinically diagnosed Alzheimer's disease (AD). However, in multi-center studies, the predictive values of the CSF biomarkers have been lower, possibly due to differences in procedures for lumbar puncture and CSF handling and storage, and to differences in patient populations, clinical evaluations, and diagnostic procedures. Here we investigate the diagnostic accuracy of CSF biomarkers in a well defined homogeneous mono-center population. We also evaluate an extended panel of amyloid related biomarkers. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants... (More)
The cerebrospinal fluid (CSF) biomarkers amyloid-beta (A beta)(1-42), T-tau, and P-tau have good diagnostic accuracy for clinically diagnosed Alzheimer's disease (AD). However, in multi-center studies, the predictive values of the CSF biomarkers have been lower, possibly due to differences in procedures for lumbar puncture and CSF handling and storage, and to differences in patient populations, clinical evaluations, and diagnostic procedures. Here we investigate the diagnostic accuracy of CSF biomarkers in a well defined homogeneous mono-center population. We also evaluate an extended panel of amyloid related biomarkers. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 32), patients with stable MCI (n = 13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n = 15), and healthy controls (n = 20). CSF was analyzed for A beta(1-42), T-tau, P-tau, A beta(X-38), A beta(X-40), A beta(X-42), sA beta PP alpha, and sA beta PP beta. In multivariate analysis, the core biomarkers A beta(1-42), T-tau, and P-tau demonstrated a high ability to diagnose AD versus the combined groups of controls and stable MCI, with an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI 0.93-1.00, p < 0.0001). The additional biomarkers only marginally increased AUROC to 0.98 (95% CI 0.95-1.00, p < 0.0001), this increase mainly mediated by A beta(X-42). In conclusion, CSF biomarkers A beta(1-42), T-tau, and P-tau have very high diagnostic accuracy in a well defined cohort of untreated patients, demonstrating the excellent potency of CSF biomarkers to identify pathological processes in AD when a stringent analytical protocol is used. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer's disease, amyloid, biomarkers, cerebrospinal fluid, diagnosis
in
Journal of Alzheimer's Disease
volume
24
issue
3
pages
537 - 546
publisher
IOS Press
external identifiers
  • wos:000292496900011
  • scopus:79957854917
ISSN
1387-2877
DOI
10.3233/JAD-2011-101878
language
English
LU publication?
yes
id
13a306a4-9503-4136-bb01-a7eb4a6b1de7 (old id 2094124)
date added to LUP
2011-09-02 08:36:33
date last changed
2017-10-22 03:11:32
@article{13a306a4-9503-4136-bb01-a7eb4a6b1de7,
  abstract     = {The cerebrospinal fluid (CSF) biomarkers amyloid-beta (A beta)(1-42), T-tau, and P-tau have good diagnostic accuracy for clinically diagnosed Alzheimer's disease (AD). However, in multi-center studies, the predictive values of the CSF biomarkers have been lower, possibly due to differences in procedures for lumbar puncture and CSF handling and storage, and to differences in patient populations, clinical evaluations, and diagnostic procedures. Here we investigate the diagnostic accuracy of CSF biomarkers in a well defined homogeneous mono-center population. We also evaluate an extended panel of amyloid related biomarkers. Sixty consecutive patients admitted for cognitive impairment to a memory clinic were recruited. The participants included patients with AD or mild cognitive impairment (MCI) diagnosed with AD upon follow-up (n = 32), patients with stable MCI (n = 13), patients with other dementias diagnosed at primary evaluation or upon follow-up (n = 15), and healthy controls (n = 20). CSF was analyzed for A beta(1-42), T-tau, P-tau, A beta(X-38), A beta(X-40), A beta(X-42), sA beta PP alpha, and sA beta PP beta. In multivariate analysis, the core biomarkers A beta(1-42), T-tau, and P-tau demonstrated a high ability to diagnose AD versus the combined groups of controls and stable MCI, with an area under the receiver operating characteristic curve (AUROC) of 0.97 (95% CI 0.93-1.00, p &lt; 0.0001). The additional biomarkers only marginally increased AUROC to 0.98 (95% CI 0.95-1.00, p &lt; 0.0001), this increase mainly mediated by A beta(X-42). In conclusion, CSF biomarkers A beta(1-42), T-tau, and P-tau have very high diagnostic accuracy in a well defined cohort of untreated patients, demonstrating the excellent potency of CSF biomarkers to identify pathological processes in AD when a stringent analytical protocol is used.},
  author       = {Johansson, Per and Mattsson, Niklas and Hansson, Oskar and Wallin, Anders and Johansson, Jan-Ove and Andreasson, Ulf and Zetterberg, Henrik and Blennow, Kaj and Svensson, Johan},
  issn         = {1387-2877},
  keyword      = {Alzheimer's disease,amyloid,biomarkers,cerebrospinal fluid,diagnosis},
  language     = {eng},
  number       = {3},
  pages        = {537--546},
  publisher    = {IOS Press},
  series       = {Journal of Alzheimer's Disease},
  title        = {Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: Diagnostic Performance in a Homogeneous Mono-Center Population},
  url          = {http://dx.doi.org/10.3233/JAD-2011-101878},
  volume       = {24},
  year         = {2011},
}