Neuronal ubiquitinated intranuclear inclusions in familial and non-familial frontotemporal dementia of the motor neuron disease type associated with amyotrophic lateral sclerosis

Eileen H. Bigio*, Nancy A. Johnson, Alfred W. Rademaker, Bing B. Fung, M. Marsel Mesulam, Nailah Siddique, Lisa Dellefave, Janice Caliendo, Stefanie Freeman, Teepu Siddique

*Corresponding author for this work

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Ubiquitinated cytoplasmic inclusions (Ub-CIs) in superficial frontal cortex and dentate gyrus neurons are the hallmark of frontotemporal degeneration of the motor neuron disease-type (FTD-MND-type). To date, 2 reports have described intranuclear ubiquitinated inclusions (Ub-INIs) in 9 cases of familial FTD-MND-type (without clinical or pathologic motor neuron disease, MND). In the current study we found an additional 11 cases with Ub-INIs. We have identified for the first time among these cases 2 with a negative family history and 3 that have concomitant amyotrophic lateral sclerosis (ALS). The results of the present study i) confirm a previous report of significantly lower average brain weight and longer duration in cases with Ub-INIs, ii) reveal significantly greater striatal neuronal loss and gliosis in cases with intranuclear inclusions, and iii) demonstrate that intranuclear inclusions correlate with cytoplasmic inclusions and dystrophic neuntes in frontal cortex and striatum but not in dentate gyrus. In addition, the current study confirms that Ub-INIs are found in familial FTD-MND-type, but also extends the presence of Ub-INIs to familial FTD-MND (with concomitant ALS), and probably also to non-familial FTD-MND-type.

Original languageEnglish (US)
Pages (from-to)801-811
Number of pages11
JournalJournal of neuropathology and experimental neurology
Volume63
Issue number8
DOIs
StatePublished - Aug 2004

Keywords

  • Amyotrophic lateral sclerosis
  • Familial dementia
  • Frontotemporal dementia
  • Frontotemporal dementia of the motor neuron disease-type
  • Motor neuron disease
  • Ubiquitin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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