ALS‐associated protein FIG4 is localized in Pick and Lewy bodies, and also neuronal nuclear inclusions, in polyglutamine and intranuclear inclusion body diseases

FIG4 is a phosphatase that regulates intracellular vesicle trafficking along the endosomal‐lysosomal pathway. Mutations of FIG4 lead to the development of C harcot ‐M arie‐ T ooth disease type 4J and amyotrophic lateral sclerosis ( ALS ). Moreover, ALS ‐associated proteins (transactivation response DNA protein 43 ( TDP ‐43), fused in sarcoma ( FUS ), optineurin, ubiquilin‐2, charged mutivesicular body protein 2b ( CHMP2B ) and valosin‐containing protein) are involved in inclusion body formation in several neurodegenerative diseases. Using immunohistochemistry, we examined the brains and spinal cords of patients with various neurodegenerative diseases, including sporadic TDP ‐43 proteinopathy ( ALS and frontotemporal lobar degeneration). TDP ‐43 proteinopathy demonstrated no FIG4 immunoreactivity in neuronal inclusions. However, FIG4 immunoreactivity was present in P ick bodies in P ick's disease, L ewy bodies in P arkinson's disease and dementia with L ewy bodies, neuronal nuclear inclusions in polyglutamine and intranuclear inclusion body diseases, and M arinesco and H irano bodies in aged control subjects. These findings suggest that FIG4 is not incorporated in TDP ‐43 inclusions and that it may have a common role in the formation or degradation of neuronal cytoplasmic and nuclear inclusions in several neurodegenerative diseases.