To investigate the effects of age, sex, APOE4, education, and amyloid deposition (via 11C PIB-PET) on the degree of regional tau deposition (via AV1451) in cognitively normal elderly.


      We identified 168 cognitively normal participants aged 52-94 years in the population-based Mayo Clinic Study of Aging who had undergone APOE4 genotyping, with Tau-PET, and PIB-PET scans available. The subjects identified had a median age of 69, 54% male, 29% APOE4 positive, median education of 16, and median PIB SUVR of 1.34. Regional uptake of Tau-PET was assessed in 46 atlas regions by summarizing the median uptake in each region scaled to the median uptake in the cerebellar crus (SUVR). For each region, we fit a linear regression model with Tau-PET SUVR as the response variable and the following potential predictor variables: global amyloid PET, age, sex, education, and APOE4 genotype. In a preliminary regional correlation analyses of PIB with Tau-PET SUVRs, we found that correlations were driven mainly by global amyloid levels. Therefore, we used global and not regional PIB SUVRs in the models presented here.


      The results are shown in Figure 1 in which each row represents an independent regional model fit and summarizes the estimated mean (95% confidence interval) difference in tau deposition for each covariate: amyloid PET, age, sex, education, and APOE4. Although effect sizes varied across regions, we found strong evidence that higher levels of amyloid were associated with increased levels of tau after accounting for age, sex, education, and APOE (p<0.01). Except in the pallidum and putamen (p<0.01), age was not independently associated with increased levels of tau. We did not see independent effects of sex, education, or APOE4 (p>0.01) in any of the regions.


      Global amyloid burden is predictive of tau deposition in a large number of brain regions after accounting for age, sex, education, and APOE4. Independent effects of age were localized to the pallidum and the putamen where non-specific Tau-PET binding has been observed.
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