Combined cut-off point determination of F-18-AV-1451 (T807) imaging biomarker for tau burden and 2018 NIA-AA definition facilitate reclassification of Alzheimer's disease
Refereed conference paper presented and published in conference proceedings


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AbstractObjectives: In 2018, the National Institute on Aging and Alzheimer’s Association (NIA-AA) updated the definition for Alzheimer’s disease (AD) to base on in vivo biomarkers of abnormal β-amyloid (Aβ) and pathologic tau deposits instead of clinical symptoms. We had previously reported a cut-off point for preclinical/clinical AD using 11C-PIB PET as a valid in vivo biomarker of Aβ plaque. We hereby, in this prospective study, evaluated the ability of 18F-AV-1451 (T807) PET, a selective tau tracer, to measure the global and regional tau burden in the brain and aimed to define a cut-off point for AD.

Methods: During Feb to Nov 2018, 43 patients (M: 17, F: 26; mean age=66.4±8.5 y, range: 50-79 y) with decreased recent memory in 1-2 years, with/without cognitive impairment, but without language dysfunction, tremor or balancing problem, prior history of stoke or other neurodegenerative diseases, were recruited into this study. They all underwent 3-tracers PET/CT: 18FDG (biomarker for prediction of future cognitive decline), 11C-PIB and T807 within 1 week. 18FDG PET was assessed visually for temporal-parietal hypometabolism. Regional and global cortical to cerebellum SUV ratios (SUVRs) were calculated for both 11C-PIB and T807 PET (35 and 85 min post injection respectively). Global SUVR on 11C-PIB PET >= 1.3 was defined as abnormal in Aβ burden. Based on 11C-PIB and 18FDG PET findings, patients were classified as: (1) 11C-PIB+ and 18FDG+ as probable-AD, (2) 11C-PIB+ and 18FDG- as AD pathologic change, (3) 11C-PIB- and 18FDG- as non-AD.

Results: According to 11C-PIB and 18FDG PET findings, 17 patients (mean age=70±6.3 y) were diagnosed as probable AD, 4 AD pathologic change (mean age=66±12.5 y) and 22 non-AD (mean age=63.7±8.6 y). Regional T807 SUVR of probable-AD patients exhibited significantly higher tau burden than non-AD patients in lateral temporal (1.45±0.29 vs 1.09±0.06), posterior cingulate (1.40±0.28 vs 1.11±0.08), medial temporal (1.38±0.17 vs 1.10±0.10), occipital (1.37±0.29 vs 1.07±0.06), precuneus (1.35±0.30 vs 1.03±0.06), superior parietal (1.28±0.31 vs 0.97±0.06) and frontal (1.22±0.21 vs 1.00±0.07) regions (all P<0.05). Global T807 binding was also significantly higher in probable-AD than non-AD patients (SUVR=1.31±0.21 vs 1.05±0.05, P<0.05). ROC curve analysis defined the cut-off point of global T807 SUVR for probable-AD as 1.14, with a sensitivity of 82.4% (14/17), specificity 95.5% (21/22), AUC 0.92. Of the 4 AD patients with pathologic change (11C-PIB+ and 18FDG-), 1 patient showed high tau burden (global SUVR=1.32), thus qualified as biological AD without neuronal injury by this new NIA-AA definition.

Conclusions: Based on the cut-off SUVR value we found for T807 tau burden, and the 2018 NIA-AA definition, 82.4% (14/17) of the probable-AD patients and 25% (1/4) of AD patients with pathologic change were reclassified as AD, while no change in classification was found in the non-AD patients. SUVR measurement of tau burden with T807 PET may also have potential in future research for severity assessment of the degree of cognitive impairment in AD patients.
All Author(s) ListHo I, Chen SR, Leung YL, Cheung MK, Ho CL, Mok V
Name of ConferenceAnnual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI)
Start Date of Conference22/06/2019
End Date of Conference25/06/2019
Place of ConferenceCalifornia
Country/Region of ConferenceUnited States of America
Journal nameJournal of Nuclear Medicine
Proceedings TitleJournal of Nuclear Medicine
Series TitleNeurosciences - Amyloid and Tau PET
Title of PublicationJOURNAL OF NUCLEAR MEDICINE
Year2019
Month5
Volume Number60
Issue NumberSuppl 1
Article number254
ISSN0161-5505
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesRadiology, Nuclear Medicine & Medical Imaging;Radiology, Nuclear Medicine & Medical Imaging

Last updated on 2021-19-09 at 00:45