Dataset Information

Diagnostic Values of Cerebrospinal Fluid T-Tau and A??? using Meso Scale Discovery Assays for Alzheimer's Disease.

ABSTRACT: Meso Scale Discovery (MSD) recently established electrochemiluminescence-based assays to measure cerebrospinal fluid (CSF) levels of total tau (t-tau) and amyloid-? 1-42 peptide (A?42) that can aid in the diagnosis of Alzheimer's disease (AD). The goal of this investigation is to independently evaluate this platform and establish cut-off values of these biomarkers for AD diagnosis.To validate the analytical and clinical performance of the MSD t-tau and A?42 kits and propose diagnostic cut-off values for the field.The analytical performance of the CSF t-tau and A?42 assays was determined, followed by assessment of diagnostic performance of CSF t-tau, A?42, and t-tau/A?42 in three clinically characterized cohorts.Both MSD assays demonstrated consistent and stable analytical performance, as well as resistance to several important pre-analytic variables. Diagnostically, t-tau/A?42 performed the best.Our results independently confirm the analytical and clinical performance of the MSD CSF t-tau and A?42 assays. Based on a large, multi-center, clinically-diagnosed cohort, we propose for the first time candidate diagnostic cut-offs for MSD measured CSF t-tau, A?42, and t-tau/A?42. However, these values needs to be refined as more subjects are included and the assays are tested by other laboratories.

SUBMITTER: Pan C

PROVIDER: S-EPMC4517668 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Diagnostic Values of Cerebrospinal Fluid T-Tau and Aβ₄₂ using Meso Scale Discovery Assays for Alzheimer's Disease.

Pan Catherine C Korff Ané A Galasko Douglas D Ginghina Carmen C Peskind Elaine E Li Ge G Quinn Joseph J Montine Thomas J TJ Cain Kevin K Shi Min M Zhang Jing J

Journal of Alzheimer's disease : JAD 20150101 3

<h4>Background</h4>Meso Scale Discovery (MSD) recently established electrochemiluminescence-based assays to measure cerebrospinal fluid (CSF) levels of total tau (t-tau) and amyloid-β 1-42 peptide (Aβ42) that can aid in the diagnosis of Alzheimer's disease (AD). The goal of this investigation is to independently evaluate this platform and establish cut-off values of these biomarkers for AD diagnosis.<h4>Objective</h4>To validate the analytical and clinical performance of the MSD t-tau and Aβ42 k ...[more]

PMID: 25613100

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Project description:ObjectiveThe primary study objective of this retrospective academic memory clinic-based observational longitudinal study was to investigate the prognostic value of a cerebrospinal fluid (CSF)-based ATN classification for subsequent cognitive decline during the 3 years following lumbar puncture in a clinical, real-life setting. The secondary objective was to investigate the prognostic value of CSF biomarkers as continuous variables.MethodsData from 228 patients (median age 67 (47-85) years), who presented at the Neurology Memory Clinic UZ/KU Leuven between September 2011 and December 2016, were included with a follow-up period of up to 36 months. Patients underwent a CSF AD biomarker test for amyloid-beta 1-42 (Aβ42), hyperphosphorylated tau (p181-tau) and total tau (t-tau) in the clinical work-up for diagnostic reasons. Patients were divided into ATN classes based on CSF biomarkers: Aβ42 for amyloid (A), p181-tau for tau (T), and t-tau as a measure for neurodegeneration (N). Based on retrospective data analysis, cognitive performance was evaluated by Mini Mental State Examination (MMSE) scores every 6 months over a period up to 36 months following the lumbar puncture. The statistical analysis was based on linear mixed-effects modeling (LME).ResultsThe distribution in the current clinical sample was as follows: A-/T-/N- 32.02%, A+/T-/N- 33.33%, A+/T+/N+ 17.11%, A+/T-/N+ 11.84%, A-/T-/N+ 4.39%, A-/T+/N+ 1.32% (3 cases), with no cases in the A-/T+/N- and A+/T+/N- class. Hence, the latter 3 classes were excluded from further analyses. The change of MMSE relative to A-/T-/N- over a 36-month period was significant in all four ATN classes: A+/T+/N+ = - 4.78 points on the MMSE; A-/T-/N+ = - 4.76; A+/T-/N+ = - 2.83; A+/T-/N- = - 1.96. The earliest significant difference was seen in the A+/T+/N+ class at 12 months after baseline. The effect of ATN class on future cognitive decline was confirmed for a different set of CSF thresholds. All individual baseline CSF biomarkers including the Aβ42/t-tau ratio showed a significant correlation with subsequent cognitive decline, with the highest correlation seen for Aβ42/t-tau.ConclusionATN classification based on CSF biomarkers has a statistically significant and clinically relevant prognostic value for the course of cognitive decline in a 3-year period in a clinical practice setting.

Project description:IntroductionThe relevance of the cerebrospinal fluid (CSF) biomarkers for the diagnosis of Alzheimer's disease (AD) and related disorders is clearly established. However, the question remains on how to use these data, which are often heterogeneous (not all biomarkers being pathologic). The objective of this study is to propose to physicians in memory clinics a biologic scale of probabilities that the patient with cognitive impairments has an Alzheimer's disease (AD) pathologic process.MethodsFor that purpose, we took advantage of the multicenter data of our Paris-North, Lille, and Montpellier (PLM) study, which has emerged through the initial sharing of information from these memory centers. Different models combining the CSF levels of amyloid-? 42, tau, and p-tau(181) were tested to generate categories of patients with very low (<10%), low (<25%), high (>75%), and very high predictive values (>90%) for positive AD. In total, 1,273 patients (646 AD and 627 non-AD) from six independent memory-clinic cohorts were included.ResultsA prediction model based on logistic regressions achieved a very good stratification of the population but had the disadvantages of needing mathematical optimization and being difficult to use in daily clinical practice. Remarkably, a simple and intuitive model based on the number (from zero to three) of three pathologic CSF biomarkers resulted in a very efficient predictive scale for AD in patients seen in memory clinics. The scale's overall predictive value for AD for the different categories were as follows: class 0, 9.6% (95% confidence interval (CI), 6.0% to 13.2%); class 1, 24.7% (95% CI, 18.0% to 31.3%); class 2, 77.2% (95% CI, 67.8% to 86.5%); and class 3, 94.2% (95% CI, 90.7% to 97.7%). In addition, with this scale, significantly more patients were correctly classified than with the logistic regression. Its superiority in model performance was validated by the computation of the net reclassification index (NRI). The model was also validated in an independent multicenter dataset of 408 patients (213 AD and 195 non-AD).ConclusionsIn conclusion, we defined a new scale that could be used to facilitate the interpretation and routine use of multivariate CSF data, as well as helping the stratification of patients in clinical research trials.

Dataset Information

Diagnostic Values of Cerebrospinal Fluid T-Tau and A??? using Meso Scale Discovery Assays for Alzheimer's Disease.

Publications

Diagnostic Values of Cerebrospinal Fluid T-Tau and Aβ₄₂ using Meso Scale Discovery Assays for Alzheimer's Disease.

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