Occurrence of basophilic inclusions and FUS-immunoreactive neuronal and glial inclusions in a case of familial amyotrophic lateral sclerosis.

Basophilic inclusions (BIs) are the pathological feature in a subset of frontotemporal lobar degeneration (FTLD), sporadic amyotrophic lateral sclerosis (SALS) and familial ALS (FALS) cases. Mutations in the fused in sarcoma (FUS) gene have been recently identified as the cause of FALS type 6. FUS-immunoreactive (ir) inclusions are consistently found in cases of FTLD with BIs, but the association between ALS cases with BIs and FUS accumulation is still not well understood. In this study, we immunohistochemically analyzed the autopsied case of FALS with BIs using anti-FUS antibodies. The case was a 42-year-old woman who developed proximal weakness of the bilateral upper limbs, followed by weakness of other parts including the bulbar regions, and died at age 45. Since this case is a member of a family with FALS harboring the R521C mutation of the FUS gene, she may have carried the same FUS mutation. Histopathologically, neuronal loss was evident in the motor system and other areas including the cuneate nucleus of the medulla oblongata. BIs appeared in the brain stem, cerebellum and anterior horn of the lumbar cord. FUS-ir neuronal cytoplasmic inclusions, glial cytoplasmic inclusions and dystrophic neurites were more abundantly and widely occurring than BIs, especially in the cuneate nucleus and globus pallidus. These findings support the idea that both BIs and FUS-ir structures are pathological hallmarks of a subset of ALS cases.