Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive 

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-26941

Neumann, M; Roeber, S; Kretzschmar, H A; Rademakers, R; Baker, M; Mackenzie, I R A (2009). Abundant FUS-immunoreactive pathology in neuronal intermediate filament inclusion disease. Acta Neuropathologica, 118(5):605-616.

[img] PDF - Registered users only
1MB

Abstract

Neuronal intermediate filament inclusion disease (NIFID) is an uncommon neurodegenerative condition that typically presents as early-onset, sporadic frontotemporal dementia (FTD), associated with a pyramidal and/or extrapyramidal movement disorder. The neuropathology is characterized by frontotemporal lobar degeneration with neuronal inclusions that are immunoreactive for all class IV intermediate filaments (IF), light, medium and heavy neurofilament subunits and alpha-internexin. However, not all the inclusions in NIFID are IF-positive and the primary molecular defect remains uncertain. Mutations in the gene encoding the fused in sarcoma (FUS) protein have recently been identified as a cause of familial amyotrophic lateral sclerosis (ALS). Because of the recognized clinical, genetic and pathological overlap between FTD and ALS, we investigated the possible role of FUS in NIFID. We found abnormal intracellular accumulation of FUS to be a consistent feature of our NIFID cases (n = 5). More neuronal inclusions were labeled using FUS immunohistochemistry than for IF. Several types of inclusions were consistently FUS-positive but IF-negative, including neuronal intranuclear inclusions and glial cytoplasmic inclusions. Double-label immunofluorescence confirmed that many cells had only FUS-positive inclusions and that all cells with IF-positive inclusions also contained pathological FUS. No mutation in the FUS gene was identified in a single case with DNA available. These findings suggest that FUS may play an important role in the pathogenesis of NIFID.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Neuropathology
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2009
Deposited On:11 Jan 2010 14:29
Last Modified:27 Nov 2013 22:46
Publisher:Springer
ISSN:0001-6322
Additional Information:The original publication is available at www.springerlink.com
Publisher DOI:10.1007/s00401-009-0581-5
PubMed ID:19669651
Citations:Web of Science®. Times Cited: 96
Google Scholar™
Scopus®. Citation Count: 111

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page