Matthew Faull1, Simon Yl Ching2, Anna I Jarmolowicz1, John Beilby2, Peter K Panegyres3. 1. Neurodegenerative Disorders Research Pty Ltd 4 Lawrence Ave, West Perth, Western Australia. 2. Department of Clinical Biochemistry, Pathwest Laboratory Medicine WA, QEII Medical Centre Nedlands, Western Australia. 3. Neurodegenerative Disorders Research Pty Ltd 4 Lawrence Ave, West Perth, Western Australia ; School of Medicine and Pharmacology, The University of Western Australia Nedlands, Western Australia.
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.
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.
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