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Published on: June 16, 2023
18F-Flortaucipir Binding in Choroid Plexus: Related to Race and Hippocampus Signal
Christopher M Lee1,2, Heidi I L Jacobs1,2,3,4, Marta Marquié5,6
1Division of Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, Boston, MA, USA.
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.
Insights
Racial differences in 18F-Flortaucipir (FTP) PET imaging may be linked to melanocyte binding in the choroid plexus (CP). Adjusting for CP signal reveals true hippocampus (HC) tau PET signal, impacting Alzheimer's disease biomarker associations.
Area of Science:
- Neurology
- Radiochemistry
- Biomarker Discovery
Background:
- 18F-Flortaucipir (FTP) PET imaging shows on-target binding to Alzheimer's disease tau aggregates.
- Off-target binding of FTP in melanocytes has been observed, particularly in the choroid plexus (CP).
Purpose of the Study:
- To investigate if CP binding is due to melanocytes by comparing signal in Black/African American (B/AA) versus White (W) participants.
- To assess the impact of CP signal spill-in on adjacent regions, specifically the hippocampus (HC).
- To determine if correcting for CP spill-in influences associations between HC FTP binding, amyloid, and cognition.
Main Methods:
- Examined FTP race differences in CP, HC, and other brain regions in 147 participants (23 B/AA, 124 W).
- Assessed spill-in effects by probing associations between CP FTP and other regions-of-interest (ROIs).
- Utilized statistical regression to adjust HC FTP measurements for CP spill-in and analyzed associations with race, cognition, and amyloid.
Main Results:
- B/AA individuals exhibited elevated CP and HC FTP signal (SUVR), but not in other ROIs or HC when adjusted for CP.
- CP FTP signal strongly correlated with HC FTP signal, suggesting spill-in effects.
- After adjusting HC FTP for CP signal, race differences disappeared, and relationships with amyloid and memory emerged.
Conclusions:
- Melanocyte-associated FTP binding in the CP may partially explain elevated CP signals.
- Off-target CP binding significantly affects HC FTP measurements, necessitating cautious interpretation.
- Correcting for CP spill-in is crucial for accurate assessment of HC tau pathology and its relationship with cognitive decline and amyloid burden.
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