The clinical and neuroanatomical phenotype of FUS associated frontotemporal lobar degeneration.

Frontotemporal lobar degeneration (FTLD) is genetically and pathologically heterogeneous. Until recently, two main pathological subtypes were recognised, defined by the presence of tau positive or tau negative, ubiquitin positive neuronal inclusions. However, the identification of TDP-43 as a major constituent of ubiquitinated inclusions led to descriptions of a smaller subgroup of patients with ubiquitin positive but TDP-43 negative pathology. Recently, the major constituent of the inclusions in such cases has been identified as FUS (‘fusedin sarcoma’) protein, implicated in RNA processing. We retrospectively reviewed all cases ascertained via a tertiary level cognitive disorders clinic between 1992 and 2009 with a clinical diagnosis of FTLD and neuropathological confirmation (post mortem or brain biopsy during life). Five of 100 patients were found to have FUS pathology (FUS1 with neuronal intermediate filament inclusion disease and four other cases with atypical FTLD with ubiquitin-positive inclusions).