%0 Journal Article %J J Alzheimers Dis %D 2018 %T 18F-Flortaucipir Binding in Choroid Plexus: Related to Race and Hippocampus Signal. %A Lee, Christopher M %A Jacobs, Heidi I L %A Marquié, Marta %A Becker, John A %A Andrea, Nicolas V %A Jin, David S %A Schultz, Aaron P %A Frosch, Matthew P %A Gómez-Isla, Teresa %A Sperling, Reisa A %A Johnson, Keith A %X

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.

%B J Alzheimers Dis %V 62 %P 1691-1702 %8 2018 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/29614677?dopt=Abstract %R 10.3233/JAD-170840 %0 Journal Article %J J Alzheimers Dis %D 2017 %T Alzheimer's Disease Biomarkers and Future Decline in Cognitive Normal Older Adults. %A Dumurgier, Julien %A Hanseeuw, Bernard J %A Hatling, Frances B %A Judge, Kelly A %A Schultz, Aaron P %A Chhatwal, Jasmeer P %A Blacker, Deborah %A Sperling, Reisa A %A Johnson, Keith A %A Hyman, Bradley T %A Gómez-Isla, Teresa %X

BACKGROUND: Identifying older adults at risk of cognitive decline represents a challenge as Alzheimer's disease (AD) modifying therapies move toward preclinical stages.

OBJECTIVE: To investigate the relationship between AD biomarkers and subsequent change in cognition in a cohort of cognitively intact older adults.

METHODS: 84 cognitively normal subjects (mean age 72.0 years, 59% women) were recruited through the Massachusetts Alzheimer's Disease Research Center and the Harvard Aging Brain Study and followed over 3 years. Measurements of amyloid-β 1-42 (Aβ42), total Tau (t-Tau), and Tau phosphorylated at threonine 181 (p-Tau181) in the cerebrospinal fluid (CSF) at study entry were available in all cases. Baseline brain MRI, FDG-PET, and PiB-PET data were available in the majority of participants. Relationship between baseline AD biomarkers and longitudinal change in cognition was assessed using Cox proportional hazard regression and linear mixed models.

RESULTS: 14% participants increased their global Clinical Dementia Rating (CDR) score from 0 to 0.5 during follow-up. A CDR score increase was associated with higher baseline CSF t-Tau and p-Tau181, higher global cortical PiB retention, and lower hippocampal volume. The combination of high CSF t-Tau and low Aβ42 or low hippocampal volume was more strongly related to cognitive outcome than each single biomarker. Higher CSF t-Tau was the only biomarker associated with subsequent decline in MMSE score.

CONCLUSIONS: Baseline CSF t-Tau and p-Tau181, in vivo amyloid load, and hippocampal volume were all independently associated with future decline in cognition. The discriminatory ability of these biomarkers to predict risk of cognitive decline, however, was only modest.

%B J Alzheimers Dis %V 60 %P 1451-1459 %G eng %N 4 %R 10.3233/JAD-170511