Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 171, Issue 1, Pages 227-240Publisher
ELSEVIER SCIENCE INC
DOI: 10.2353/ajpath.2007.070182
Keywords
-
Categories
Funding
- NIA NIH HHS [P01 AG003991, AG12300, AG05681, P50 AG005681, AG03991, AG16976, AG17586, AG13854, U01 AG016976, P30 AG012300, P30 AG013854, P30 AG010124, AG10124, P01 AG017586] Funding Source: Medline
Ask authors/readers for more resources
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 (FMs) 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 fainthal FTLD-U with and without MND and expand this disease spectrum to include reported families with FTD linked to chromosome 9p but not FM 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available