Fine structural analysis of the neuronal inclusions of frontotemporal lobar degeneration with TDP-43 proteinopathy

Thorpe, Julian R, Tang, Helen, Atherton, Joe and Cairns, Nigel J (2008) Fine structural analysis of the neuronal inclusions of frontotemporal lobar degeneration with TDP-43 proteinopathy. Journal of Neural Transmission, 115. pp. 1661-1671.

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Abstract

TAR DNA-binding protein of 43 kDa (TDP-43) is a major component of the pathological inclusions of frontotemporal lobar degeneration with TDP-43 proteinopathy, also called FTLD with ubiquitin-positive, tau-negative inclusions (FTLD-U), and motor neuron disease (MND). TDP-43 is predominantly expressed in the nucleus and regulates gene expression and splicing. In FTLD with TDP-43 proteinopathy, neuronal inclusions present variably as cytoplasmic inclusions (NCIs), dystrophic neurites (DNs), and intranuclear inclusions (NIIs), leading to a fourfold neuropathological classification correlating with genotype. There have been few fine structural studies of these inclusions. Thus, we undertook an immunoelectron microscopic study of FTLD with TDP-43 proteinopathy, including sporadic and familial cases with progranulin (GRN) mutation. TDP-43-immunoreactive inclusions comprised two components: granular and filamentous. Filament widths, expressed as mean (range) were: NCI, 9 nm (416 nm); DN, 10 nm (516 nm); NII, 18 nm (950 nm). Morphologically distinct inclusion components may reflect the process of TDP-43 aggregation and interaction with other proteins: determining these latter may contribute towards understanding the heterogeneous pathogenesis of FTLD with TDP-43 proteinopathy.

Item Type: Article
Schools and Departments: School of Life Sciences > Biochemistry
Depositing User: Julian Thorpe
Date Deposited: 06 Feb 2012 20:17
Last Modified: 22 Mar 2012 11:53
URI: http://srodev.sussex.ac.uk/id/eprint/25188
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