首页 | 本学科首页   官方微博 | 高级检索  
     


TDP-43 in familial and sporadic frontotemporal lobar degeneration with ubiquitin inclusions
Authors:Cairns Nigel J  Neumann Manuela  Bigio Eileen H  Holm Ida E  Troost Dirk  Hatanpaa Kimmo J  Foong Chan  White Charles L  Schneider Julie A  Kretzschmar Hans A  Carter Deborah  Taylor-Reinwald Lisa  Paulsmeyer Katherine  Strider Jeffrey  Gitcho Michael  Goate Alison M  Morris John C  Mishra Manjari  Kwong Linda K  Stieber Anna  Xu Yan  Forman Mark S  Trojanowski John Q  Lee Virginia M-Y  Mackenzie Ian R A
Affiliation:MRCPath, Department of Pathology and Immunology, Washington University School of Medicine, Campus Box 8118, St Louis, MO 63110, USA. cairns@wustl.edu
Abstract:TAR DNA-binding protein 43 (TDP-43) is a major pathological protein of sporadic and familial frontotemporal lobar degeneration with ubiquitin-positive, tau-negative inclusions (FTLD-U) with or without motor neuron disease (MND). Thus, TDP-43 defines a novel class of neurodegenerative diseases called TDP-43 proteinopathies. We performed ubiquitin and TDP-43 immunohistochemistry on 193 cases of familial and sporadic FTLD with or without MND. On selected cases, immunoelectron microscopy and biochemistry were performed. Clinically defined frontotemporal dementias (FTDs) included four groups: 1) familial FTD with mutations in progranulin (n = 36), valosin-containing protein (n = 5), charged multivesicular body protein 2B (n = 4), and linked to chromosome 9p (n = 7); 2) familial cases of FTD with unknown gene association (n = 29); 3) sporadic FTD (n = 72); and 4) familial and sporadic FTD with MND (n = 40). Our studies confirm that the spectrum of TDP-43 proteinopathies includes most cases of sporadic and familial FTLD-U with and without MND and expand this disease spectrum to include reported families with FTD linked to chromosome 9p but not FTD with charged multivesicular body protein 2B mutations. Thus, despite significant clinical, genetic, and neuropathological heterogeneity of FTLD-U, TDP-43 is a common pathological substrate underlying a large subset of these disorders, thereby implicating TDP-43 in novel and unifying mechanisms of FTLD pathogenesis.
Keywords:
本文献已被 PubMed 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号