Longitudinal [18F]RO948 PET SUVR is associated with Aβ accumulation and baseline tau pathology: Neuroimaging / differential diagnosis.

Background: Alzheimer's disease (AD) is defined by amyloid‐β (Aβ) and tau pathology. Specifically, Aβ and tau are thought to interact, with Aβ mediating the spread of tau. We here aimed to examine the association between cross‐sectional Aβ and tau‐PET with change in tau‐PET SUVR. Methods: 51 subjects from the ongoing BioFINDER‐2 longitudinal sub‐study were included: 23 cognitively unimpaired (CU; 9 Aβ‐negative,14 Aβ‐positive), 21 with MCI (3 Aβ‐negative,18 Aβ‐positive) and 7 AD with dementia (all Aβ‐positive). Aβ‐status was based on CSF Aβ42/Aβ40. Aβ (CU, MCI only, by design) and tau‐PET (all subjects) were performed using [18F]flutemetamol and [18F]RO948, respectively. Subjects underwent a targeted follow‐up of ∼12‐months (mean=13.2±2.6) with [18F]RO948. FreeSurfer (v.6.0) was used to calculate mean‐SUVR values for tau‐PET across four predefined ROIs reflecting Braak‐stages I‐VI (inferior cerebellar cortex as reference). For Aβ‐PET SUVR, a cortical meta‐ROI was used (composite white‐matter reference region). The association between longitudinal and cross‐sectional findings was assessed using linear regression with subject specific slopes for tau‐PET and tau and Aβ‐PET SUVR at baseline as predictors (adjusted for age, sex, interscan‐interval). Results: Largest longitudinal change and effect‐sizes followed a group/Braak ROI specific pattern (Figure 1): I‐II (entorhinal cortex) for Aβ‐positive CU (+3.14%, effect‐size 0.72), III‐IV (amygdala, fusiform gyrus, inferior/middle temporal cortex, and parahippocampus) for Aβ‐positive MCI (+3.62%, effect‐size 0.61) and V‐VI (neocortical) for AD dementia (+3.98%, effect‐size 0.58). No significant increases were seen across Aβ‐negative subjects. Regression models in CU and MCI subjects (no AD dementia due absence of Aβ‐PET) showed that increases in tau‐PET SUVR were related to both Aβ‐PET and tau‐PET SUVR at baseline. However, when incorporating both measures as predictors, Aβ‐PET remained significant only in Aβ‐positive CU subjects. Plotting change in tau‐PET as a function of change in Aβ‐PET (Figure 2) revealed a seeming threshold effect whereby tau pathology accelerated around an Aβ‐PET SUVR of 0.65. Conclusion: Initial results with longitudinal [18F]RO948 indicate that it is able to capture the progression of early tau pathology in Aβ‐positive CU subjects, as well as cortical increases in subjects with cognitive impairment. A critical burden of Aβ appears to be a prerequisite for increases in tau pathology. [ABSTRACT FROM AUTHOR]