TY - JOUR
T1 - Comparing ATN-T designation by tau PET visual reads, tau PET quantification, and CSF PTau181 across three cohorts
AU - Provost, Karine
AU - Iaccarino, Leonardo
AU - Soleimani-Meigooni, David N.
AU - Baker, Suzanne
AU - Edwards, Lauren
AU - Eichenlaub, Udo
AU - Hansson, Oskar
AU - Jagust, William
AU - Janabi, Mustafa
AU - la Joie, Renaud
AU - Lesman-Segev, Orit
AU - Mellinger, Taylor J.
AU - Miller, Bruce L.
AU - Ossenkoppele, Rik
AU - Pham, Julie
AU - Smith, Ruben
AU - Sonni, Ida
AU - Strom, Amelia
AU - Mattsson-Carlgren, Niklas
AU - For the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
AU - Rabinovici, Gil D.
N1 - Funding Information: This study was supported by the National Institute on Aging grants (P30-AG062422 to B.L.M and G.D.R., P01-AG019724 to B.L.M., R01-AG-045611 to G.D.R.), Alzheimer’s Association (AARF-16-443577 to R.L.J., AACSF-19-617663 to D.N.S.-M.), and Rainwater Charitable Foundation (Tau Consortium) (to G.D.R. and W.J.J.). Avid Radiopharmaceuticals enabled use of the Flortaucipir tracer, and Roche Diagnostics provided the Elecsys kits for CSF analysis; Avid Radiopharmaceuticals and Roche Diagnostics did not provide direct funding and was not involved in data analysis or interpretation. COBAS, COBAS E, and ELECSYS are trademarks of Roche. Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: AbbVie, Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; Araclon Biotech; BioClinica, Inc.; Biogen; Bristol-Myers Squibb Company; CereSpir, Inc.; Cogstate; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; EuroImmun; F. Hoffmann-La Roche Ltd. and its affiliated company Genentech, Inc.; Fujirebio; GE Healthcare; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Lumosity; Lundbeck; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Neurotrack Technologies; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Takeda Pharmaceutical Company; and Transition Therapeutics. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health ( www.fnih.org ). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Therapeutic Research Institute at the University of Southern California. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7
Y1 - 2021/7
N2 - Purpose: To compare rates of tau biomarker positivity (T-status) per the 2018 Alzheimer’s Disease (AD) Research Framework derived from [18F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181). Methods: We included 351 subjects with varying clinical diagnoses from three cohorts with available FTP PET and CSF PTau181 within 18 months. T-status was derived from (1) FTP visual assessment by two blinded raters; (2) FTP standardized uptake value ratio (SUVR) quantification from a temporal meta-ROI (threshold: SUVR ≥1.27); and (3) Elecsys® Phospho-Tau (181P) CSF (Roche Diagnostics) concentrations (threshold: PTau181 ≥ 24.5 pg/mL). Results: FTP visual reads yielded the highest rates of T+, while T+ by SUVR increased progressively from cognitively normal (CN) through mild cognitive impairment (MCI) and AD dementia. T+ designation by CSF PTau181 was intermediate between FTP visual reads and SUVR values in CN, similar to SUVR in MCI, and lower in AD dementia. Concordance in T-status between modality pairs ranged from 68 to 76% and varied by clinical diagnosis, being highest in patients with AD dementia. In discriminating Aβ + MCI and AD subjects from healthy controls and non-AD participants, FTP visual assessment was most sensitive (0.96) but least specific (0.60). Specificity was highest with FTP SUVR (0.91) with sensitivity of 0.89. Sensitivity (0.73) and specificity (0.72) were balanced for PTau181. Conclusion: The choice of tau biomarker may differ by disease stage and research goals that seek to maximize sensitivity or specificity. Visual interpretations of tau PET enhance sensitivity compared to quantification alone, particularly in early disease stages.
AB - Purpose: To compare rates of tau biomarker positivity (T-status) per the 2018 Alzheimer’s Disease (AD) Research Framework derived from [18F]flortaucipir (FTP) PET visual assessment, FTP quantification, and cerebrospinal fluid (CSF) phosphorylated Tau-181 (PTau181). Methods: We included 351 subjects with varying clinical diagnoses from three cohorts with available FTP PET and CSF PTau181 within 18 months. T-status was derived from (1) FTP visual assessment by two blinded raters; (2) FTP standardized uptake value ratio (SUVR) quantification from a temporal meta-ROI (threshold: SUVR ≥1.27); and (3) Elecsys® Phospho-Tau (181P) CSF (Roche Diagnostics) concentrations (threshold: PTau181 ≥ 24.5 pg/mL). Results: FTP visual reads yielded the highest rates of T+, while T+ by SUVR increased progressively from cognitively normal (CN) through mild cognitive impairment (MCI) and AD dementia. T+ designation by CSF PTau181 was intermediate between FTP visual reads and SUVR values in CN, similar to SUVR in MCI, and lower in AD dementia. Concordance in T-status between modality pairs ranged from 68 to 76% and varied by clinical diagnosis, being highest in patients with AD dementia. In discriminating Aβ + MCI and AD subjects from healthy controls and non-AD participants, FTP visual assessment was most sensitive (0.96) but least specific (0.60). Specificity was highest with FTP SUVR (0.91) with sensitivity of 0.89. Sensitivity (0.73) and specificity (0.72) were balanced for PTau181. Conclusion: The choice of tau biomarker may differ by disease stage and research goals that seek to maximize sensitivity or specificity. Visual interpretations of tau PET enhance sensitivity compared to quantification alone, particularly in early disease stages.
KW - Alzheimer’s disease
KW - Biomarkers
KW - CSF
KW - Flortaucipir
KW - PET
KW - Tau
UR - http://www.scopus.com/inward/record.url?scp=85098793440&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00259-020-05152-8
DO - https://doi.org/10.1007/s00259-020-05152-8
M3 - Article
C2 - 33398408
SN - 1619-7070
VL - 48
SP - 2259
EP - 2271
JO - European journal of nuclear medicine and molecular imaging
JF - European journal of nuclear medicine and molecular imaging
IS - 7
ER -