¹⁸F-Flortaucipir Binding in Choroid Plexus: Related to Race and Hippocampus Signal

Article type: Research Article

Authors: Lee, Christopher M.^{a; b; 1} | Jacobs, Heidi I.L.^{a; b; h; i; 1} | Marquié, Marta^{c; e} | Becker, John A.^{a; b} | Andrea, Nicolas V.^{a; b} | Jin, David S.^{a; b} | Schultz, Aaron P.^{b; d} | Frosch, Matthew P.^{c; e; f; h} | Gómez-Isla, Teresa^{c; e; h} | Sperling, Reisa A.^{c; d; g; h} | Johnson, Keith A.^{a; b; c; g; h; *}

Affiliations: [a] Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA | [b] Department of Radiology, Massachusetts General Hospital, Boston, MA, USA | [c] Department of Neurology, Massachusetts General Hospital, Boston, MA, USA | [d] The Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA, USA | [e] MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Boston, MA, USA | [f] C.S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Boston, MA, USA | [g] Department of Neurology, Center for Alzheimer Research and Treatment, Brigham and Women’s Hospital, Boston, MA, USA | [h] Harvard Medical School, Boston, MA, USA | [i] School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Alzheimer Center Limburg, Maastricht University, Maastricht, The Netherlands

Correspondence: [*] Correspondence to: Dr. Keith Johnson, MD, Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. Tel.: +1 617 724 7066; Fax: +1 617 724 5123; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

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.

Keywords: Alzheimer’s disease, choroid plexus, off-target binding, melanin, race, tau PET

DOI: 10.3233/JAD-170840

Journal: Journal of Alzheimer's Disease, vol. 62, no. 4, pp. 1691-1702, 2018