Amyloid-PET, tau-PET, and their association in sporadic early-onset Alzheimer’s Disease: Cross-sectional and longitudinal data from the LEADS study

Abstract

BackgroundWe aimed to describe amyloid- and tau-PET in patients with sporadic Early Onset AD (sEOAD) from the Longitudinal Early-onset Alzheimer’s Disease Study. We focused on amyloid-tau relationships and on the association between i) age, sex, and ii) cross-sectional and longitudinal PET measures.MethodsIn December 2022, we selected patients who fulfilled the following criteria: 1) clinical diagnosis of MCI or mild dementia, 2) available amyloid-PET (18F-florbetaben), tau-PET (18F-fortaucipir), and structural MRI, 3) positive amyloid-PET based on a process including visual read and quantification. Image acquisition, quality control, and processing followed ADNI procedures. Florbetaben-PET Centiloids and mean cortical Flortaucipir-SUVR were extracted in native space using FreeSurfer. Cross-sectional analyses were performed using general linear models; longitudinal analyses (up to 4 scans/patient) were performed using linear mixed effect models with random intercepts.ResultsOut of the 372 cognitively impaired patients included in LEADS, 280 (75.3%) were amyloid-positive patients with sEOAD (Table 1 for demographics and clinical characteristics). Cross-sectionally, Centiloids and cortical Flortaucipir-SUVR were correlated (r = 0.29, p<.001; Fig 1a). Patient’s age was associated with cortical tau-PET (older patients showing lower Flortaucipir-SUVR, r = -0.47, p<0.001, Fig 1b) but not amyloid-PET (r = -0.02, p = 0.68). Females showed greater amyloid (d = 0.43, p<0.001, Fig 1c) and tau-PET burden (d = 0.35, p = 0.004), in the absence of sex differences in MMSE or CDR-SB (d’s<0.16, p’s>0.37). Sex differences in tau-PET remained significant (p = 0.04) when controlling for age and Centiloids. Both Centiloids and Flortaucipir-SUVR increased longitudinally (p<0.001, Figure 3a-b). The rate of Centiloid change was not modulated by age (time*age, p = 0.79) or sex (time*sex, p = 0.91). Changes in tau-PET were independent of sex (time*sex, p = 0.15), but younger patients tended to show greater FTP-SUVR progression (time*age, p = 0.07). In a subsample of 123 patients with at least 2 timepoints for both amyloid and tau-PET (Fig 3c), rates of amyloid and tau changes were correlated (r = 0.22, p = 0.013).ConclusionIn patients with sEOAD, amyloid- and tau-PET are modestly correlated at baseline and continue to increase together over time. In EOAD, younger age is associated with higher tau-PET burden, independent of amyloid. Females show greater amyloid and tau burden than males despite similar clinical severity measures.