Altered brain structure in a mouse model of ALS with mutation in Tardbp is observed from early adulthood

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by aggregates of TDP-43 in the brain. The TDP-M323K mouse model of ALS has a mutation in Tardbp and presents progressive motor, neurological and behavioural phenotypes, in addition to widespread changes in brain volume at 12 months of age. Here, we assessed if these volumetric changes are progressive or if they are already present before other symptoms start to present. Post-mortem structural MRI in 3- and 12 months-old TDP-M323K mice revealed that brain volume is already altered in young adults despite the absence of major clinical and pathological phenotypes.