Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study
Version 2 2020-08-27, 12:13
Version 1 2020-06-16, 03:44
Posted on 2020-08-27 - 12:13
Abstract Background The objective of this study was to make a quantitative comparison of flortaucipir PET retention with pathological tau and β-amyloid across a range of brain regions at autopsy. Methods Patients with dementia (two with clinical diagnosis of AD, one undetermined), nearing the end of life, underwent 20-min PET, beginning 80 min after an injection of ~370 mBq flortaucipir [18F]. Neocortical, basal ganglia, and limbic tissue samples were obtained bilaterally from 19 regions at autopsy and subject-specific PET regions of interest corresponding to the 19 sampled target tissue regions in each hemisphere were hand drawn on the PET images. SUVr values were calculated for each region using a cerebellar reference region. Abnormally phosphorylated tau (Ptau) and amyloid-β (Aβ) tissue concentrations were measured for each tissue region with an antibody capture assay (Histelide) using AT8 and H31L21 antibodies respectively. Results The imaging-to-autopsy interval ranged from 4–29 days. All three subjects had intermediate to high levels of AD neuropathologic change at autopsy. Mean cortical SUVr averaged across all three subjects correlated significantly with the Ptau immunoassay (Pearson r = 0.81; p < 0.0001). When Ptau and Aβ1-42 were both included in the model, the Ptau correlation with flortaucipir SUVr was preserved but there was no correlation of Aβ1-42 with flortaucipir. There was also a modest correlation between limbic (hippocampal/entorhinal and amygdala) flortaucipir SUVr and Ptau (Pearson r = 0.52; p < 0.080). There was no significant correlation between SUVr and Ptau in basal ganglia. Conclusions The results of this pilot study support a quantitative relationship between cortical flortaucipir SUVr values and quantitative measures of Ptau at autopsy. Additional research including more cases is needed to confirm the generalizability of these results. Trial registration, NIH Clinicaltrials.gov NCT # 02516046. Registered August 27, 2015. https://clinicaltrials.gov/ct2/show/NCT02516046?term=02516046&draw=2&rank=1
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Pontecorvo, Michael J.; Keene, C. Dirk; Beach, Thomas G.; Montine, Thomas J.; Arora, Anupa K.; Devous, Michael D.; et al. (2020). Comparison of regional flortaucipir PET with quantitative tau immunohistochemistry in three subjects with Alzheimer’s disease pathology: a clinicopathological study. figshare. Collection. https://doi.org/10.6084/m9.figshare.c.5022521.v2
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AUTHORS (22)
MP
Michael J. Pontecorvo
CK
C. Dirk Keene
TB
Thomas G. Beach
TM
Thomas J. Montine
AA
Anupa K. Arora
MD
Michael D. Devous
MN
Michael Navitsky
IK
Ian Kennedy
AJ
Abhinay D. Joshi
ML
Ming Lu
GS
Geidy E. Serrano
LS
Lucia I. Sue
AI
Anthony J. Intorcia
SR
Shannon E. Rose
AW
Angela Wilson
LH
Leanne Hellstern
NC
Natalie Coleman
MF
Matthew Flitter
PA
Patricia Aldea
AF
Adam S. Fleisher