Spatial patterns of phosphorylated TDP-43-immunoreactive cellular inclusions in familial and sporadic frontotemporal lobar degeneration with TDP-43 proteinopathy

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  • Richard A Armstrong

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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.


Publication date2016
Publication titleHorizons in neurological research
EditorsAndres Costa, Eugenio Villalba
Place of PublicationHauppage, NJ (US)
PublisherNova science
Number of pages23
ISBN (Electronic)978-1-63485-287-6
ISBN (Print)978-1-63485-286-9
Original languageEnglish

Publication series

NameHorizons 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

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