Karine Provost1, Leonardo Iaccarino2, David N Soleimani-Meigooni2,3, Suzanne Baker3, Lauren Edwards2, Udo Eichenlaub4, Oskar Hansson5, William Jagust3,6, Mustafa Janabi3, Renaud La Joie2, Orit Lesman-Segev2, Taylor J Mellinger2, Bruce L Miller2, Rik Ossenkoppele5,7, Julie Pham2, Ruben Smith5, Ida Sonni3,8, Amelia Strom2, Niklas Mattsson-Carlgren5,9,10, Gil D Rabinovici2,3,6,11. 1. Memory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94143, USA. provost.karine@gmail.com. 2. Memory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94143, USA. 3. Lawrence Berkeley National Laboratory, Berkeley, CA, USA. 4. Roche Diagnostics GmbH, Penzberg, Germany. 5. Clinical Memory Research Unit, Lund University, Lund, Sweden. 6. Helen Wills Neuroscience Institute, UC Berkeley, Berkeley, CA, USA. 7. Alzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands. 8. Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, UC Los Angeles, Los Angeles, CA, USA. 9. Department of Neurology, Skåne University Hospital, Lund, Sweden. 10. Wallenberg Centre for Molecular Medicine, Lund University, Lund, Sweden. 11. Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.
Abstract
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.
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.
Entities:
Keywords:
Alzheimer’s disease; Biomarkers; CSF; Flortaucipir; PET; Tau
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