Author: Andrew Alexander, Brecca Bettcher, Bradley T Christian, Jose Guerrero-Gonzalez, Steven Kecskemeti, Lisette LeMerise, Max McLachlan, Andrew McVea, Matthew Zammit 👨🔬
Affiliation: University of Wisconsin-Madison School of Medicine and Public Health and Waisman Center 🌍
Purpose: Individuals with Down syndrome (DS) develop Alzheimer’s Disease (AD) with very high prevalence (>90%). Neuropathology includes amyloid plaque (Aβ) accumulation, followed by neurofibrillary tau tangles in the mesial temporal cortex. These misfolded proteins may induce inflammation and white matter (WM) degeneration. Diffusion tensor imaging (DTI) is sensitive to WM microstructural changes using water diffusion. Tauopathy is associated with changes in neuroinflammation and neurodegeneration, which would increase water diffusion and decrease diffusion anisotropy in affected WM. Tau-PET standard uptake value ratio (SUVR) was used to identify positivity (T+) in the temporal lobe to investigate a multimodal approach for detecting the impact of tau on WM. This study explores the relationship between mesial temporal T+ and DTI in DS.
Methods: Multimodality scans of DTI, tau, and amyloid-PET from n=60 participants with DS (age: 26-57-yrs) were included from the ABC-DS study. Amyloid burden was measured in centiloids (CL) and T+ was determined with a 1.4 SUVR cutoff. DTI parameters included fractional anisotropy (FA) and mean, radial, and axial diffusivities (MD, RD, AD). Tract-based spatial statistics extracted a WM skeleton in a DS-specific common space. After image preprocessing and DTI calculation, individual DTI data were projected onto the skeleton, and permutation analysis of linear models evaluated group differences in DTI parameters between T+ and T- participants, accounting for age and CL: DTI=β0+(βagexAge)+(βCLxCL)+(βTau-groupxTau-group) Significant regions (p<0.05, FWE-corrected) were localized using a WM atlas.
Results: MD, RD, and AD showed significant regional effects, with higher values in the T+ group, suggesting WM microstructure changes are associated with tauopathy. MD and RD showed ore widespread effects, including the long association fibers, forceps major, corona radiate, and corpus callosum.
Conclusion: These findings suggest that medial temporal tau is impactful beyond its local vicinity, identifying regions for monitoring response to anti-amyloid interventions. Future work will explore longitudinal measurements.