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

Yi Mo, Julie Stromswold, Kimberly Wilson, Daniel Holder, Cyrille Sur, Omar Laterza, Mary J. Savage, Arie Struyk, Philip Scheltens, Charlotte E. Teunissen, James Burke, S. Lance Macaulay, Geir Bråthen, Sigrid Botne Sando, Linda R. White, Christy Weiss, Arturo Cowes, Michele M. Bush, Ganga DeSilva, David G. DarbyStephanie R. Rainey-Smith, Jackie Surls, Eileen Sagini, Michael Tanen, Amy Altman, Johan Luthman, Michael F. Egan*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction Changes 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. Methods A 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. Results A 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. Discussion A 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.

Original languageEnglish
Pages (from-to)201-209
Number of pages9
JournalAlzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring
Volume6
DOIs
Publication statusPublished - 1 Jan 2017

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