Extensive FUS-immunoreactive pathology in juvenile amyotrophic lateral sclerosis with basophilic inclusions

Eric J. Huang, Jiasheng Zhang, Felix Geser, John Q. Trojanowski, Jonathan B. Strober, Dennis W Dickson, Robert H. Brown, Barbara E. Shapiro, Catherine Lomen-Hoerth

Research output: Contribution to journalArticle

99 Citations (Scopus)

Abstract

Juvenile amyotrophic lateral sclerosis (ALS) with basophilic inclusions is a well-recognized entity. However, the molecular underpinnings of this devastating disease are poorly understood. Here, we present genetic and neuropathological characterizations in two young women with fatal rapidly progressive ALS with basophilic inclusions. In one case, a germline mutation (P525L) was detected in the fused in sarcoma/translocated in liposarcoma (FUS/TLS) gene, whereas no mutation was identified in the other case. Postmortem examination in both cases revealed severe loss of spinal motor neurons with remaining neurons showing basophilic inclusions that contain abnormal aggregates of FUS proteins and disorganized intracellular organelles, including mitochondria and endoplasmic reticulum. In both patients, the FUS-positive inclusions were also detected in neurons in layers IVV of cerebral cortex and several brainstem nuclei. In contrast, spinal motor neurons in patients with late-onset sporadic ALS showed no evidence of abnormal accumulation of FUS protein. These results underscore the importance of FUS mutations and pathology in rapidly progressive juvenile ALS. Furthermore, our study represents the first detailed characterizations of neuropathological findings in rapidly progressive juvenile ALS patients with a mutation in the FUS/TLS gene.

Original languageEnglish (US)
Pages (from-to)1069-1076
Number of pages8
JournalBrain Pathology
Volume20
Issue number6
DOIs
StatePublished - Nov 2010
Externally publishedYes

Fingerprint

Amyotrophic Lateral Sclerosis
RNA-Binding Protein FUS
Pathology
Liposarcoma
Motor Neurons
Sarcoma
Mutation
Neurons
Germ-Line Mutation
Endoplasmic Reticulum
Organelles
Cerebral Cortex
Genes
Brain Stem
Autopsy
Mitochondria

Keywords

  • ALS
  • electron microscopy
  • FUS
  • immunohistochemistry
  • mutation

ASJC Scopus subject areas

  • Neuroscience(all)
  • Pathology and Forensic Medicine
  • Clinical Neurology

Cite this

Extensive FUS-immunoreactive pathology in juvenile amyotrophic lateral sclerosis with basophilic inclusions. / Huang, Eric J.; Zhang, Jiasheng; Geser, Felix; Trojanowski, John Q.; Strober, Jonathan B.; Dickson, Dennis W; Brown, Robert H.; Shapiro, Barbara E.; Lomen-Hoerth, Catherine.

In: Brain Pathology, Vol. 20, No. 6, 11.2010, p. 1069-1076.

Research output: Contribution to journalArticle

Huang, EJ, Zhang, J, Geser, F, Trojanowski, JQ, Strober, JB, Dickson, DW, Brown, RH, Shapiro, BE & Lomen-Hoerth, C 2010, 'Extensive FUS-immunoreactive pathology in juvenile amyotrophic lateral sclerosis with basophilic inclusions', Brain Pathology, vol. 20, no. 6, pp. 1069-1076. https://doi.org/10.1111/j.1750-3639.2010.00413.x
Huang, Eric J. ; Zhang, Jiasheng ; Geser, Felix ; Trojanowski, John Q. ; Strober, Jonathan B. ; Dickson, Dennis W ; Brown, Robert H. ; Shapiro, Barbara E. ; Lomen-Hoerth, Catherine. / Extensive FUS-immunoreactive pathology in juvenile amyotrophic lateral sclerosis with basophilic inclusions. In: Brain Pathology. 2010 ; Vol. 20, No. 6. pp. 1069-1076.
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