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Concordance between cerebrospinal fluid biomarkers with Alzheimer’s disease pathology between three independent assay platforms

Doecke, J.D., Rembach, A., Villemagne, V.L., Varghese, S., Rainey-Smith, S., Sarros, S., Evered, L.A., Fowler, C.J., Pertile, K.K., Rumble, R.L., Trounson, B., Taddei, K., Laws, S.M., Macaulay, S.L., Bush, A.I., Ellis, K.A., Martins, R., Ames, D., Silbert, B., Vanderstichele, H., Masters, C.L., Darby, D.G., Li, Q-X, Collins, S. and Kuiperij, H.B. (2017) Concordance between cerebrospinal fluid biomarkers with Alzheimer’s disease pathology between three independent assay platforms. Journal of Alzheimer's disease : JAD, 61 (1). pp. 169-183.

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Background:To enhance the accuracy of clinical diagnosis for Alzheimer’s disease (AD), pre-mortem biomarkers have become increasingly important for diagnosis and for participant recruitment in disease-specific treatment trials. Cerebrospinal fluid (CSF) biomarkers provide a low-cost alternative to positron emission tomography (PET) imaging for in vivo quantification of different AD pathological hallmarks in the brains of affected subjects; however, consensus around the best platform, most informative biomarker and correlations across different methodologies are controversial. Objective:Assessing levels of Aβ-amyloid and tau species determined using three different versions of immunoassays, the current study explored the ability of CSF biomarkers to predict PET Aβ-amyloid (32 Aβ-amyloid–and 45 Aβ-amyloid+), as well as concordance between CSF biomarker levels and PET Aβ-amyloid imaging. Methods:Prediction and concordance analyses were performed using a sub-cohort of 77 individuals (48 healthy controls, 15 with mild cognitive impairment, and 14 with AD) from the Australian Imaging Biomarker and Lifestyle study of aging. Results:Across all three platforms, the T-tau/Aβ42 ratio biomarker had modestly higher correlation with SUVR/BeCKeT (ρ= 0.69–0.8) as compared with Aβ42 alone (ρ= 0.66–0.75). Differences in CSF biomarker levels between the PET Aβ-amyloid–and Aβ-amyloid+ groups were strongest for the Aβ42/Aβ40 and T-tau/Aβ42 ratios (p < 0.0001); however, comparison of predictive models for PET Aβ-amyloid showed no difference between Aβ42 alone and the T-tau/Aβ42 ratio. Conclusion:This study confirms strong concordance between CSF biomarkers and PET Aβ-amyloid status is independent of immunoassay platform, supporting their utility as biomarkers in clinical practice for the diagnosis of AD and for participant enrichment in clinical trials.

Item Type: Journal Article
Publisher: IOS Press
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