Abnormal protein aggregates of transactive response (TAR) DNA-binding protein (TDP-43) in the form of neuronal cytoplasmic inclusions (NCI), oligodendroglial inclusions (GI), neuronal internuclear inclusions (NII), and dystrophic neurites (DN) are the pathological hallmark of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP). To investigate the role of phosphorylated TDP-43 (pTDP-43) in neurodegeneration in FTLD-TDP, the spatial patterns of the pTDP-43-immunoreactive NCI, GI, NII, and DN were studied in frontal and temporal cortex in three groups of cases: (1) familial FTLD-TDP caused by progranulin (GRN) mutation, (2) a miscellaneous group of familial cases containing cases caused by valosin-containing protein (VCP) mutation, ubiquitin associated protein 1 (UBAP1) mutation, and cases not associated with currently known genes, and (3) sporadic FTLD-TDP. In a significant number of brain regions, the pTDP-43-immunoreactive inclusions developed in clusters and the clusters were distributed regularly parallel to the tissue boundary. The spatial patterns of the inclusions were similar to those revealed by a phosphorylation-independent anti-TDP-43 antibody. The spatial patterns and cluster sizes of the pTDP-43-immunoreactive inclusions were similar in GRN mutation cases, remaining familial cases, and in sporadic FTLD-TDP. Hence, pathological changes initiated by different genetic factors in familial cases and by unknown causes in sporadic FTLD-TDP appear to follow a parallel course resulting in very similar patterns of degeneration of frontal and temporal lobes.
|Title of host publication||Horizons in neurological research|
|Editors||Andres Costa, Eugenio Villalba|
|Place of Publication||Hauppage, NJ (US)|
|Number of pages||23|
|Publication status||Published - 2016|
|Name||Horizons in Neurological Research|
- frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP)
- TAR DNA-binding protein of 43 kDa (TDP-43)
- neuronal cytoplasmic inclusions (NCI)
- phosphorylation-dependent anti-TDP-43 antibody (pTDP-43)
- spatial pattern
Armstrong, R. A. (2016). Spatial patterns of phosphorylated TDP-43-immunoreactive cellular inclusions in familial and sporadic frontotemporal lobar degeneration with TDP-43 proteinopathy. In A. Costa, & E. V. (Eds.), Horizons in neurological research (Vol. 25, pp. 59-82). (Horizons in Neurological Research; Vol. 25). Nova science.