A multinational study distinguishing Alzheimer's and healthy patients using cerebrospinal fluid tau/Aβ42 cutoff with concordance to amyloid positron emission tomography imaging
Mary J. Savage
Charlotte E. Teunissen
S. Lance Macaulay
Sigrid Botne Sando
Linda R. White
Michele M. Bush
David G. Darby
Stephanie Rainey-Smith, Edith Cowan UniversityFollow
Michael F. Egan
Centre of Excellence for Alzheimer's Disease Research and Care
Merck & Co., Inc., Kenilworth, NJ, USA
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.
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.
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.
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.
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Mo, Y., Stromswold, J., Wilson, K., Holder, D., Sur, C., Laterza, O., ... & Burke, J. (2017). A multinational study distinguishing Alzheimer's and healthy patients using cerebrospinal fluid tau/Aβ42 cutoff with concordance to amyloid positron emission tomography imaging. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 6, 201-209.