Past Event: Oden Institute Seminar

The multiphysics of prion-like disease: Spreading and atrophy of neurodegeneration

Ellen Kuhl, Professor, Mechanical Engineering, Stanford University

Abstract

Neurodegeneration will undoubtedly become a major challenge in medicine and public health because of demographic changes worldwide. More than 45 million people are living with dementia today and this number is expected to triple by 2050. Recent studies have reinforced the hypothesis that the prion paradigm--the templated growth and spreading of misfolded proteins--could help explain the progression of a variety of neurodegenerative disorders. However, our current understanding of prion-like growth and spreading is rather empirical. Here we show that a physics-based reaction-diffusion model can explain the growth and spreading of misfolded protein in a variety of neurodegenerative disorders. We combine the classical Fisher-Kolmogorov equation for population dynamics with anisotropic diffusion and simulate misfolding across a representative section of the brain and across the brain as a whole. Our model correctly predicts amyloid-beta deposits and tau inclusions in Alzheimer's disease, alpha-synuclein inclusions in Parkinson's disease, and TDP-43 inclusions in amyotrophic lateral sclerosis. Our results suggest that misfolded proteins in various neurodegenerative disorders grow and spread according to a universal law that follows the basic physical principles of nonlinear reaction and anisotropic diffusion. A more quantitative understanding of the timeline of neurodegeneration could have important clinical implications, ranging from estimating the socioeconomic burden of neurodegeneration to designing clinical trials and pharmacological intervention. Bio Ellen Kuhl is a Professor of Mechanical Engineering at Stanford University. She received her PhD from the University of Stuttgart in 2000 and her Habilitation from the University of Kaiserslautern in 2004. Her area of expertise is Living Matter Physics, the design of theoretical and computational models to predict the acute and chronic behavior of living structures. Ellen has published more than 200 peer-reviewed journal articles and edited two books; she is an active reviewer for more than 20 journals at the interface of engineering and medicine and an editorial board member of seven international journals in her field. Ellen is currently the Chair of the US National Committee on Biomechanics, an Executive Member of the US Association for Computational Mechanics, and the Chair of the Biomechanical Engineering Group at Stanford. She is a Fellow of the American Institute for Mechanical and Biological Engineering and a founding member of the Living Heart Project, a translational research initiative to revolutionize cardiovascular science through realistic simulation. Ellen received the National Science Foundation Career Award in 2010, was selected as Midwest Mechanics Seminar Speaker in 2014, and received the Humboldt Research Award in 2016.