Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Dec 5;3(3):143-51.
eCollection 2014.

Comparison of two methods for the analysis of CSF Aβ and tau in the diagnosis of Alzheimer's disease

Affiliations

Comparison of two methods for the analysis of CSF Aβ and tau in the diagnosis of Alzheimer's disease

Matthew Faull et al. Am J Neurodegener Dis. .

Abstract

Introduction: Biomarkers represent a promising adjunct to clinical techniques in the diagnosis of Alzheimer's Disease (AD) and other neurodegenerative diseases. At present, the potential of cerebrospinal fluid (CSF) biomarkers in diagnosing AD has been suggested but the degree of clinical utility is yet to be defined due to variability between studies. In this paper we compare the performance of two cerebrospinal fluid assay methods in predicting clinically diagnosed AD.

Methods: CSF biomarker concentrations for Aβ1-42, P-tau181P and T-tau were analysed using INNOTEST (ELISA) and INNO-BIA AlzBio3 (Luminex) assay methods from Innogenetics, Belgium. Patients were clinically diagnosed based on NINCDS-ADRDA criteria supplemented with structural MRI, (18)F-fluorodeoxy-glucose positron emission tomography (FDG-PET) and cognitive profiling.

Results: An abnormally low Aβ1-42 was the most useful biomarker in predicting clinical AD. Depending on the assay method, the predictive accuracy remained constant or improved slightly when abnormalities in P-tau181P and T-tau were considered in addition to Aβ1-42. The Luminex method with our optimised reference concentrations performed best for patients ≤ 65 years with sensitivity = 1 and a specificity = 0.60 for both Aβ1-42 and when one or more abnormal biomarkers were considered.

Conclusion: Given accurate, robust and reproducible CSF analytical methods, of which the Luminex method seems the most useful and practicable, our investigation suggests that measuring CSF Aβ1-42, P-tau and T-tau has utility in the diagnosis of probable AD and, when used with clinical diagnostic techniques, seems especially helpful in the diagnosis of AD with onset prior to the age of 65 years.

Keywords: Alzheimer’s disease; P-tau; T-tau; amyloid beta; biomarkers; cerebrospinal fluid; clinical diagnosis; tau.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Flowchart of patient enrolment for CSF analysis.
Figure 2
Figure 2
CSF biomarker concentrations for ELISA and Luminex assay methods for all patients. Horizontal lines represent mean ± standard deviation.
Figure 3
Figure 3
Linear regression: relationship between ELISA and Luminex CSF biomarker concentrations.

References

    1. Hampel H, Lista S, Khachaturian ZS. Development of biomarkers to chart all Alzheimer’s disease stages: the royal road to cutting the therapeutic Gordian Knot. Alzheimers Dement. 2012;8:312–36. - PubMed
    1. Kang JH, Vanderstichele H, Trojanowski JQ, Shaw LM. Simultaneous analysis of cerebrospinal fluid biomarkers using microsphere-based xMAP multiplex technology for early detection of Alzheimer’s disease. Methods. 2012;56:484–93. - PubMed
    1. Mattsson N, Zetterberg H. Alzheimer’s disease and CSF biomarkers: key challenges for broad clinical applications. Biomark Med. 2009;3:735–7. - PubMed
    1. Perrin RJ. Cerebrospinal fluid biomarkers for clinical trials: why markers for differential diagnosis are important. Arch Neurol. 2012;69:1407–8. - PubMed
    1. Hampel H, Lista S. Use of biomarkers and imaging to assess pathophysiology, mechanisms of action and target engagement. J Nutr Health Aging. 2013;17:54–63. - PubMed

LinkOut - more resources