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FUS/TLS-immunoreactive neuronal and glial cell inclusions increase with disease duration in familial amyotrophic lateral sclerosis with an R521C FUS/TLS mutation.
- Source :
-
Journal of neuropathology and experimental neurology [J Neuropathol Exp Neurol] 2012 Sep; Vol. 71 (9), pp. 779-88. - Publication Year :
- 2012
-
Abstract
- Basophilic inclusions (BIs) are pathological features of a subset of frontotemporal lobar degeneration disorders, including sporadic amyotrophic lateral sclerosis (ALS) and familial ALS (FALS). Mutations in the fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene have recently been identified as a cause of FALS. The FUS/TLS-immunoreactive inclusions are consistently found in cases of frontotemporal lobar degeneration with BIs; however, the association between ALS cases with BIs and FUS/TLS accumulation is not well understood. We used immunohistochemistry to analyze 3 autopsy cases of FALS with the FUS/TLS mutation and with BIs using anti-FUS/TLS antibodies. The disease durations were 1, 3, and 9 years. As the disease duration becomes longer, there were broader distributions of neuronal and glial FUS/TLS-immunoreactive inclusions. As early as 1 year after the onset, BIs, neuronal cytoplasmic inclusions and glial cytoplasmic inclusions were found in the substantia nigra in addition to the anterior horn of the spinal cord. Glial cytoplasmic inclusions are found earlier and in a wider distribution than neuronal cytoplasmic inclusions. The distribution of FUS/TLS-immunoreactive inclusions in FUS/TLS-mutated FALS with BIs was broader than that of BIs alone, suggesting that the pathogenetic mechanism may have originated from the FUS/TLS proteinopathy.
- Subjects :
- Adult
Arginine genetics
Brain pathology
Cysteine genetics
DNA Mutational Analysis
DNA-Binding Proteins metabolism
Disease Progression
Female
Humans
Male
Neuroglia metabolism
Neurons metabolism
Ubiquitin metabolism
Amyotrophic Lateral Sclerosis classification
Amyotrophic Lateral Sclerosis genetics
Amyotrophic Lateral Sclerosis metabolism
Amyotrophic Lateral Sclerosis pathology
Inclusion Bodies pathology
Mutation, Missense genetics
Neuroglia pathology
Neurons pathology
RNA-Binding Protein FUS genetics
RNA-Binding Protein FUS metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1554-6578
- Volume :
- 71
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- Journal of neuropathology and experimental neurology
- Publication Type :
- Academic Journal
- Accession number :
- 22878663
- Full Text :
- https://doi.org/10.1097/NEN.0b013e318264f164