A multinational study distinguishing Alzheimer's and healthy patients using cerebrospinal fluid tau/Aβ42 cutoff with concordance to amyloid positron emission tomography imaging

Abstract

IntroductionChanges in cerebrospinal fluid (CSF) tau and amyloid β (Aβ)42 accompany development of Alzheimer's brain pathology. Robust tau and Aβ42 immunoassays were developed to establish a tau/Aβ42 cutoff distinguishing mild-to-moderate Alzheimer's disease (AD) subjects from healthy elderly control (HC) subjects.MethodsA CSF tau/Aβ42 cutoff criteria was chosen, which distinguished the groups and maximized concordance with amyloid PET. Performance was assessed using an independent validation cohort.ResultsA tau/Aβ42 = 0.215 cutoff provided 94.8% sensitivity and 77.7% specificity. Concordance with PET visual reads was estimated at 86.9% in a ∼50% PET positive population. In the validation cohort, the cutoff demonstrated 78.4% sensitivity and 84.9% specificity to distinguish the AD and HC populations.DiscussionA tau/Aβ42 cutoff with acceptable sensitivity and specificity distinguished HC from mild-to-moderate AD subjects and maximized concordance to brain amyloidosis. The defined cutoff demonstrated that CSF analysis may be useful as a surrogate to imaging assessment of AD pathology.

A Longitudinal Study of Total and Phosphorylated α-Synuclein with Other Biomarkers in Cerebrospinal Fluid of Alzheimer’s Disease and Mild Cognitive Impairment

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Targeted mass spectrometry to quantify brain-derived cerebrospinal fluid biomarkers in Alzheimer’s disease

“…The last logistic regression classifier was trained to classify a biological profile suggestive of AD using an amyloid/tau ratio CSF cutoff. A total of 67 samples (Akesogen) were included in the Aβ/Tau ratio analyses using a ratio threshold for AD biomarker positivity of 4.6 as previously reported [23]. These three logistic regression classifiers for each protein were trained using a five-fold cross validation procedure and the performance of these classifiers was assessed on the testing set using the AUC of the ROC curve (Additional file 1: Table S9).…”

The impact of preanalytical variables on measuring cerebrospinal fluid biomarkers for Alzheimer's disease diagnosis: A review

“…Considerable work has been done to standardize CSF biomarker measurement across different assays and laboratories. Notable efforts include: 1) the development of certified reference materials for the CSF biomarkers, currently underway within the International Federation of Clinical Chemistry Working Group for CSF proteins [75], 2) the introduction of reference measurement procedures (RMPs) based on liquid chromatography tandem mass spectrometry for CSF Aβ(1-42) quantification, which were recently formally certified by the Joint Committee for Traceability in Laboratory Medicine (C11RMP9 and C12RMP1, respectively) [76,77], and 3) the establishment of quality control programs for monitoring between-laboratory and between-batch variability of commercially available immunoassays [28,72,[78][79][80][81][82].…”