Journal
JOURNAL OF ALZHEIMERS DISEASE
Volume 62, Issue 4, Pages 1691-1702Publisher
IOS PRESS
DOI: 10.3233/JAD-170840
Keywords
Alzheimer's disease; choroid plexus; off-target binding; melanin; race; tau PET
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Funding
- NIH National Institute on Aging [R01 AG046396, P01 AG036694, P50 AG00513421, AG005134, AG036694]
- Fidelity Biosciences, Harvard Neurodiscovery Center, Alzheimer's Association, Alzheimer Nederland [WE.15-2014-06]
- ASISA Foundation, Madrid, Spain
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Background: On target F-18-Flortaucipir (FTP) binding of Alzheimer's disease tau aggregates and off-target binding of melanocytes have been demonstrated with autoradiography. Objective: We aimed to investigate the hypothesis that if binding in choroid plexus (CP) is due to melanocytes, the signal would be elevated in Black/African American (B/AA) compared to White (W) participants. In addition, we examined whether CP signal affects measurements in adjacent regions, and whether correcting for spill-in effects has an influence on associations between hippocampus (HC) FTP and amyloid or cognition. Methods: FTP race differences in 147 Harvard Aging Brain Study participants (23 B/AA, 124W) were examined in CP, HC, HC covaried for CP, amygdala, inferior temporal gyrus, entorhinal cortex, and fusiform regions. Associations between CP FTP and other regions-of-interest (ROIs) were probed to assess spill-in effects. A statistical regression approach to attenuate CP spill-in was tested by relating adjusted HC SUVR residuals and unadjusted HC SUVR to race, cognition and amyloid. All analyses were covaried for age, sex, education and amyloid deposition, and Bonferroni-corrected for multiple comparisons. Results: B/AA individuals had elevated CP and HC SUVR (p < 0.007), whereas other ROI SUVR and HC SUVR covaried for CP SUVR did not show race differences (p > 0.05). CP SUVR was associated with HC SUVR (p< 10(-14)), but with no other ROI SUVR (p > 0.05). When adjusting HC SUVR for CP SUVR, no race differences in residual HC SUVR were detected, and relationships with amyloid and memory became apparent. Conclusion: Melanocyte FTP binding may account partially for high CP signal. This off-target binding affects mainly HC FTP measurements, which should be interpreted with caution.
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