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Modeling neurodegeneration in chronic traumatic encephalopathy using gradient damage models

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Abstract

Chronic traumatic encephalopathy is a progressive neurodegenerative disorder that results from repetitive impacts to the head. Its distinguishing feature is an accumulation of abnormal tau proteins in characteristic regions within the brain. Histopathological studies reveal that tau consistently localizes at the depth of cerebral sulci; yet, the mechanistic origin of this pattern remains unclear. Here we show that a continuum damage model, enhanced with nonlocal gradients, can explain the initial distribution of abnormal tau proteins. We hypothesize that tau aggregation is associated with neuronal death, which we represent as tissue softening and stiffness degradation. Our simulations correctly identify the initial locations of tau deposition, at the depth of cerebral sulci, from where damage spreads within the cortical layer and then across the entire brain. Our computational model has the potential to provide a mechanistic explanation of the stereotypic histopathology of chronic traumatic encephalopathy and predict the cumulative effects of repeated mild traumatic brain injuries.

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Acknowledgements

This study was supported by a postdoctoral fellowship from the Belgian American Educational Foundation (BAEF) and a Duesberg postdoctoral fellowship from the University of Liège to Lise Noël and by the NSF Grant CMMI 1727268 Understanding Neurodegeneration across the Scales to Ellen Kuhl.

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  1. Department of Mechanical Engineering, Stanford University, Stanford, CA, 94305, USA

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Noël, L., Kuhl, E. Modeling neurodegeneration in chronic traumatic encephalopathy using gradient damage models. Comput Mech 64, 1375–1387 (2019). https://doi.org/10.1007/s00466-019-01717-z

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