Abstract #1208

Anatomical and microstructural brain alterations in the TDP-M323K mouse model of amyotrophic lateral sclerosis

Aurea B Martins-Bach¹, Mohamed Tachrount¹, Cristiana Tisca¹, Lily Qiu¹, Shoshana Spring², Jacob Ellegood², Brian J Nieman², John G. Sled², Remya Raghavan-Nair ³, Elizabeth Fisher⁴, Thomas Cunningham³, Jason Lerch¹, and Karla Miller¹

¹Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, United Kingdom, ²Mouse Imaging Centre, The Hospital for Sick Children, Toronto, ON, Canada, ³Mammalian Genetics Unit, MRC Harwell Institute, Oxford, United Kingdom, ⁴Department of Neuromuscular Diseases, Institute of Neurology, University College London, London, United Kingdom

Amyotrophic lateral sclerosis is a devastating neurodegenerative disease, characterized by aggregates of TDP-43 protein in the brain of most patients. The TDP-M323K mouse has a mutation in the gene encoding the Tdp-43 protein, and presents progressive motor and neurological phenotypes. In this study, we assessed structural and microstructural alterations in the brain of TDP-M323K mice with preclinical MRI (7 tesla). High resolution images showed brain atrophy, but relative volume changes included hypertrophy in the cortex and hippocampus. Diffusion MRI revealed alterations compatible with neurodegeneration in the white matter and striatum. TDP-M323K mice recapitulate brain imaging phenotypes observed in ALS patients.

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