[Clinical and pathological characteristics of FUS/TLS-associated amyotrophic lateral sclerosis (ALS)].

FUS/TLS is identified as the causative gene of ALS6. FUS/TLS shares a role in nuclear protein as RNA editing with TDP43, and aggregates in basophilic inclusions (BIs) in ALS6 as well as juvenile ALS with BIs. FUS/TLS is also associated with atypical frontotemporal lobar degeneration (aFTLD), neuronal intermediate inclusion body disease (NIBD) and basophilic inclusion body disease (BIBD). Thus, FUS/TLS as well as TDP43 may provide clues to motor neuron disease (MND) and frontotemoporal dementia (FTD). We have established consortium to study MND/FTD in collaboration with neurological, psychiatric and geriatric institutes. Two clinically sporadic ALS-FUS/TLS cases were selected from the consortium: a case of ALS6 without family history and a case of juvenile ALS with BIs. Both cases presented with BIs, which were immunoreactive for anti-FUS/TLS antibodies and ultrastructurally consisted of granulofilamentous profiles common to ubiquitin-immunoreactive inclusions. Two familial ALS6 cases were also studied in the consortium. Biochemical analysis showed no truncation, phosphorylation or ubiquitination of FUS in insoluble fraction, that shows clear difference from TDP43. The mechanism of FUSopathy is currently a challenging theme from the point of protein aggregation.