title: Motor neuron disease: biomarker development for an expanding cerebral syndrome.
abstract: Descriptions of motor neuron disease (MND) documented more than a century ago remain instantly recognisable to the physician. The muscle weakness, typically with signs of upper and lower motor neuron dysfunction, is uniquely relentless. Over the last 30 years, a wider cerebral pathology has emerged, despite the lack of overt cognitive impairment in the majority of patients. From the initial linkage of a small number of cases to mutations in SOD1, diverse cellular pathways have been implicated in pathogenesis. An increasingly complex clinical heterogeneity has emerged around a significant variability in survival. Defining a cellular signature of aggregated TDP-43 common to nearly all MND and a large proportion of frontotemporal dementia (FTD), has placed MND alongside more traditional cerebral neurodegeneration. With new genetic causes, most notably a hexanucleotide expansion in C9orf72 associated with both MND and FTD, the development of biomarkers against which to test therapeutic candidates is a priority.
authors.affiliation: Medical Research Council senior clinical fellow, Nuffield Department of Clinical Neurosciences, University of Oxford, UK martin.turner@ndcn.ox.ac.uk.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Turner
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D057180:Frontotemporal Dementia; D006801:Humans; D016472:Motor Neuron Disease / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers
keywords: Amyotrophic lateral sclerosis; biomarker; frontotemporal dementia; genetics; pathology