FUS‐immunoreactive inclusions are a common feature in sporadic and non‐SOD1 familial amyotrophic lateral sclerosis
Annals of neurology, 2010•Wiley Online Library
Objective Amyotrophic lateral sclerosis (ALS) is a fatal disorder of motor neuron
degeneration. Most cases of ALS are sporadic (SALS), but about 5 to 10% of ALS cases are
familial (FALS). Recent studies have shown that mutations in FUS are causal in
approximately 4 to 5% of FALS and some apparent SALS cases. The pathogenic
mechanism of the mutant FUS‐mediated ALS and potential roles of FUS in non‐FUS ALS
remain to be investigated. Methods Immunostaining was performed on postmortem spinal …
degeneration. Most cases of ALS are sporadic (SALS), but about 5 to 10% of ALS cases are
familial (FALS). Recent studies have shown that mutations in FUS are causal in
approximately 4 to 5% of FALS and some apparent SALS cases. The pathogenic
mechanism of the mutant FUS‐mediated ALS and potential roles of FUS in non‐FUS ALS
remain to be investigated. Methods Immunostaining was performed on postmortem spinal …
Objective
Amyotrophic lateral sclerosis (ALS) is a fatal disorder of motor neuron degeneration. Most cases of ALS are sporadic (SALS), but about 5 to 10% of ALS cases are familial (FALS). Recent studies have shown that mutations in FUS are causal in approximately 4 to 5% of FALS and some apparent SALS cases. The pathogenic mechanism of the mutant FUS‐mediated ALS and potential roles of FUS in non‐FUS ALS remain to be investigated.
Methods
Immunostaining was performed on postmortem spinal cords from 78 ALS cases, including SALS (n = 52), ALS with dementia (ALS/dementia, n = 10), and FALS (n = 16). In addition, postmortem brains or spinal cords from 22 cases with or without frontotemporal lobar degeneration were also studied. In total, 100 cases were studied.
Results
FUS‐immunoreactive inclusions were observed in spinal anterior horn neurons in all SALS and FALS cases, except for those with SOD1 mutations. The FUS‐containing inclusions were also immunoreactive with antibodies to TDP43, p62, and ubiquitin. A fraction of tested FUS antibodies recognized FUS inclusions, and specific antigen retrieval protocol appeared to be important for detection of the skein‐like FUS inclusions.
Interpretation
Although mutations in FUS account for only a small fraction of FALS and SALS, our data suggest that FUS protein may be a common component of the cellular inclusions in non‐SOD1 ALS and some other neurodegenerative conditions, implying a shared pathogenic pathway underlying SALS, non‐SOD1 FALS, ALS/dementia, and related disorders. Our data also indicate that SOD1‐linked ALS may have a pathogenic pathway distinct from SALS and other types of FALS. ANN NEUROL 2010;67:739–748
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