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Fine structural analysis of the neuronal inclusions of frontotemporal lobar degeneration with TDP-43 proteinopathy
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posted on 2023-06-08, 05:46 authored by Julian R Thorpe, Helen Tang, Joe Atherton, Nigel J CairnsTAR 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.
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- Published
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Journal of Neural TransmissionPublisher URL
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115Page range
1661-1671Department affiliated with
- Biochemistry Publications
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- Yes
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2012-02-06Usage metrics
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