Tau propagation out of the MTL areas to the isocortex is facilitated by the presence of amyloid

• Published in: Alzheimer's & dementia Vol. 19; no. S17
• Main Authors: Garbarino, Sara, Campi, Cristina, Pardini, Matteo
• Format: Journal Article
• Language: English
• Published: 01.12.2023
• ISSN: 1552-5260; 1552-5279
• DOI: 10.1002/alz.071901

Background Amyloid and tau proteins are known pathological signatures of Alzheimer’s disease. Tau in particular spreads in the brains following stereotypical spatiotemporal patterns which seem to be mediated by brain connectivity. Novel imaging techniques allow visualisation of in vivo tau distribution and, in combination with state‐of‐the‐art computational tools, provide new insights into its dynamics. Method We propose a network diffusion model to describe tau evolution from longitudinal Positron Emission Tomography data of 872 subjects from the Alzheimer’s Disease Neuroimaging Initiative. The model accounts for time‐ and region‐dependent production, clearance, propagation and saturation terms. Tau dynamics is enforced “trans‐synaptically” over an ideal healthy anatomical connectome. We use Bayesian inference, providing a tool for simulation and prediction of tau deposition and its dynamics parameters along its progression. We fit the model on 2 datasets: “amyloid+” and “amyloid‐“ (identified based on Ab42 levels in the CSF; 338 and 534 subjects respectively). Result The estimated tau progression and dynamic parameters show that propagation of tau out of the MTL areas (middle/inferior‐temporal; entorhinal; hippocampal) to the isocortex is facilitated by the presence of amyloid (Figures 1‐3) and progresses along the connectomes. Indeed, amyloid+ subjects show, on average, a progression of tau that (i) accumulates earlier in the entorhinal, hippocampal and MTL areas than amyloid‐ subjects; and (ii) reaches the isocortex within the estimated 25‐years progression window by propagating along the connections between the MTL areas and the isocortex (esp. frontal and parietal). Conclusion This supports the hypothesis that regional amyloid‐tau interactions in MTL promote onset and acceleration of AD tau spreading.