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Cerebrospinal fluid biomarkers for Alzheimer’s disease: diagnostic performance in a homogeneous mono-center population.

Abstract

The cerebrospinal fluid (CSF) biomarkers amyloid-β (Aβ)(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 Aβ(1-42), T-tau, and P-tau, and PA(X-38), Aβ(X-40), Aβ(X-42), sAβPPα, and sAβPPβ. In multivariate analysis, thecore biomarkers Aβ(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 Aβ(X-42). In conclusion, CSF biomarkers Aβ(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 astringent analytical protocol is used.

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  • Authors+Show Affiliations

    ,

    Department of Neuropsychiatry, Skaraborg Hospital, Falköping, Sweden.

    , , , , , , ,

    Source

    MeSH

    Aged
    Alzheimer Disease
    Amyloid beta-Peptides
    Apolipoprotein E4
    Biomarkers
    Cognition Disorders
    Enzyme-Linked Immunosorbent Assay
    Female
    Humans
    Male
    Middle Aged
    Neuropsychological Tests
    Peptide Fragments
    ROC Curve
    Statistics, Nonparametric
    tau Proteins

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21297262

    Citation

    Johansson, Per, et al. "Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: Diagnostic Performance in a Homogeneous Mono-center Population." Journal of Alzheimer's Disease : JAD, vol. 24, no. 3, 2011, pp. 537-46.
    Johansson P, Mattsson N, Hansson O, et al. Cerebrospinal fluid biomarkers for Alzheimer’s disease: diagnostic performance in a homogeneous mono-center population. J Alzheimers Dis. 2011;24(3):537-46.
    Johansson, P., Mattsson, N., Hansson, O., Wallin, A., Johansson, J. O., Andreasson, U., ... Svensson, J. (2011). Cerebrospinal fluid biomarkers for Alzheimer’s disease: diagnostic performance in a homogeneous mono-center population. Journal of Alzheimer's Disease : JAD, 24(3), pp. 537-46. doi:10.3233/JAD-2011-101878.
    Johansson P, et al. Cerebrospinal Fluid Biomarkers for Alzheimer’s Disease: Diagnostic Performance in a Homogeneous Mono-center Population. J Alzheimers Dis. 2011;24(3):537-46. PubMed PMID: 21297262.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cerebrospinal fluid biomarkers for Alzheimer’s disease: diagnostic performance in a homogeneous mono-center population. AU - Johansson,Per, AU - Mattsson,Niklas, AU - Hansson,Oskar, AU - Wallin,Anders, AU - Johansson,Jan-Ove, AU - Andreasson,Ulf, AU - Zetterberg,Henrik, AU - Blennow,Kaj, AU - Svensson,Johan, PY - 2011/2/8/entrez PY - 2011/2/8/pubmed PY - 2011/9/20/medline SP - 537 EP - 46 JF - Journal of Alzheimer's disease : JAD JO - J. Alzheimers Dis. VL - 24 IS - 3 N2 - The cerebrospinal fluid (CSF) biomarkers amyloid-β (Aβ)(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 Aβ(1-42), T-tau, and P-tau, and PA(X-38), Aβ(X-40), Aβ(X-42), sAβPPα, and sAβPPβ. In multivariate analysis, thecore biomarkers Aβ(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 Aβ(X-42). In conclusion, CSF biomarkers Aβ(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 astringent analytical protocol is used. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/21297262/Cerebrospinal_fluid_biomarkers_for_Alzheimer’s_disease:_diagnostic_performance_in_a_homogeneous_mono_center_population_ L2 - https://content.iospress.com/openurl?genre=article&amp;id=doi:10.3233/JAD-2011-101878 DB - PRIME DP - Unbound Medicine ER -