Non-invasive in vivo neuropathology of the C9orf72-related ALS-FTD syndrome

The unmistakeable neurodegenerative disease amyotrophic lateral sclerosis (ALS) is a common clinical endpoint for an expanding range of upstream cellular pathway derangements. Clinical, genetic and molecular signatures shared with frontotemporal dementia (FTD) have rendered the brain axiomatic to ALS pathology; a core feature of what is a motor and para-motor multi-system degeneration, rather than a secondary after-thought over-shadowed by the more visible consequences of peripheral lower motor neuron loss. For the emerging era of therapy for neurodegenerative disorders to flourish, tools that can assess pathology at the system as well as cellular level are essential. In this issue, Floeter and colleagues demonstrate the potential of advanced structural MRI of the brain in this respect, exploring the relationship of white matter tract integrity using diffusion tensor imaging (DTI) to clinical parameters in a genetically homogeneous but clinically heterogeneous group of individuals carrying the C9orf72 repeat expansio