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The Impact of Cerebrospinal Fluid Biomarkers on the Diagnosis of Alzheimer’s Disease

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Abstract

The cerebrospinal fluid (CSF) biomarkers β-amyloid1–42 (Aβ1–42), total tau protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181P) are gradually finding their way into routine clinical practice as an affirmative diagnostic tool for Alzheimer’s disease (AD). These biomarkers have also been implemented in the revised diagnostic criteria for AD.

The combination of the CSF biomarkers Aβ1–42, T-tau, and P-tau181P leads to high (around 80%) levels of sensitivity, specificity, and diagnostic accuracy for discrimination between AD and controls (including psychiatric disorders like depression) and can be applied for diagnosing AD in the predementia phases of the disease (mild cognitive impairment). The added value of CSF biomarkers could lie within those cases in which the clinical diagnostic work-up is not able to discriminate between AD and non-AD dementias. However, their discriminatory power for the differential diagnosis of dementia is suboptimal. Other CSF biomarkers, especially those that are reflective of the pathology of non-AD dementia etiologies, could improve the accuracy of differential dementia diagnosis.

CSF biomarkers will be of help to establish a correct and early AD diagnosis, even in the preclinical stages of the disease, which will be of importance once disease-modifying drugs for AD become available. Variation in biomarker measurements still jeopardize the introduction of CSF biomarkers into routine clinical practice and clinical trials, but several national and international standardization initiatives are ongoing.

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Acknowledgments

Research performed by the authors was supported by the Special Research Fund of the University of Antwerp; the Foundation for Alzheimer Research (SAO-FRMA); the Institute Born-Bunge; the agreement between the Institute Born-Bunge and the University of Antwerp; the central Biobank facility of the Institute Born-Bunge/University of Antwerp; the Fund for Scientific Research-Flanders (FWO–V); the Interuniversity Attraction Poles (IAP) Program P6/43 of the Belgian Federal Science Policy Office; and the Methusalem Excellence Grant of the Flemish Government, Belgium.

Sebastiaan Engelborghs and Nathalie Le Bastard have served as advisory board members for Innogenetics NV. The authors report no conflicts of interest that are directly relevant to the content of this article.

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Authors and Affiliations

  1. Reference Center for Biological Markers of Dementia (BIODEM), Institute Born-Bunge, University of Antwerp, Universiteitsplein 1, BE-2610, Antwerpen, Belgium

    Sebastiaan Engelborghs & Nathalie Le Bastard

  2. Department of Neurology and Memory Clinic, Hospital Network Antwerp (ZNA) Middelheim and Hoge Beuken, Antwerp, Belgium

    Sebastiaan Engelborghs

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  1. Sebastiaan Engelborghs
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  2. Nathalie Le Bastard
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Correspondence to Sebastiaan Engelborghs.

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Engelborghs, S., Le Bastard, N. The Impact of Cerebrospinal Fluid Biomarkers on the Diagnosis of Alzheimer’s Disease. Mol Diagn Ther 16, 135–141 (2012). https://doi.org/10.1007/BF03262201

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