Christopher M Lee1,2, Heidi I L Jacobs1,2,3,4, Marta Marquié5,6, John A Becker1,2, Nicolas V Andrea1,2, David S Jin1,2, Aaron P Schultz2,7, Matthew P Frosch5,6,8,3, Teresa Gómez-Isla5,6,3, Reisa A Sperling5,7,9,3, Keith A Johnson1,2,5,9,3. 1. Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA. 2. Department of Radiology, Massachusetts General Hospital, Boston, MA, USA. 3. Harvard Medical School, Boston, MA, USA. 4. School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands. 5. Department of Neurology, Massachusetts General Hospital, Boston, MA, USA. 6. MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Boston, MA, USA. 7. The Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA. 8. C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA, USA. 9. Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Boston, MA, USA.
Abstract
BACKGROUND: On target 18F-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.
BACKGROUND: On target 18F-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.
Entities:
Keywords:
Alzheimer’s disease; choroid plexus; melanin; off-target binding; race; tau PET
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