PET-MEASURED PROGRESSION OF TAU PATHOLOGY ACROSS IN-VIVO STAGES OF REGIONAL AMYLOID DEPOSITION
- Alexis Moscoso, Sweden
Abstract
Aims
Previous research has consistently found widespread tau aggregation in the presence of global amyloid-β (Aβ) pathology, but it remains unclear at what level of Aβ burden tau pathology accelerates. Here, we studied cross-sectional and longitudinal tau aggregation in relation to progressive stages of regional Aβ deposition as determined by a recently established PET-based staging approach.
Methods
We examined 424 subjects from the Alzheimer’s Disease Neuroimaging Initiative with concurrent T1 MRI, 18F-Florbetapir-PET (FBP), and 18F-Flortaucipir-PET (FTP) scans. 151 participants underwent at least one longitudinal FTP scan over a mean follow-up time of 1.6 years. A previously developed PET staging method for FBP was used to stratify participants into 4 progressive stages of regional Aβ deposition. Cross-sectional and longitudinal patterns of regional tau aggregation across Aβ stages were examined using multiple linear regression and mixed models, respectively, adjusted for age, sex, and clinical diagnosis.
Results
In accordance with previous findings, individual Aβ deposition patterns followed a highly consistent regional hierarchy that allowed staging >99% of individuals into one of four progressive Aβ stages. In cross-sectional analyses, only Aβ stages III and IV revealed elevated tau deposition in temporal, parietal, and frontal cortices compared to stage 0 (FDR<0.05). Confirming these cross-sectional findings, only stages III and IV showed faster longitudinal tau accumulation rates in the aforementioned areas (Fig. 1-3).
Conclusions
The induction of more severe and widespread tau pathology seems to occur at advanced stages of Aβ deposition, which only covers a subpopulation of Aβ-positive individuals as conventionally defined.