Effect of topographical distribution of α-synuclein pathology on TDP-43 accumulation in Lewy body disease View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2010-12

AUTHORS

Osamu Yokota, Yvonne Davidson, Tetsuaki Arai, Masato Hasegawa, Haruhiko Akiyama, Hideki Ishizu, Seishi Terada, Stephen Sikkink, Stuart Pickering-Brown, David M. A. Mann

ABSTRACT

It has been reported that the development of TDP-43 pathology in cases of Lewy body disease (LBD) might be associated with the severity of tau pathology. However, the impact of α-synuclein pathology on TDP-43 accumulation in LBD remains unclear. To clarify whether α-synuclein pathology has an effect on TDP-43 accumulation, independent of tau pathology, we examined by immunohistochemistry 56 cases of LBD using a phosphorylation-dependent TDP-43 antibody. The frequency of TDP-43 pathology in all LBD cases was 18% (10/56). In 37 LBD cases with no or low tau burden (LBD-Ltau; Braak NFT stages 0-II), the frequency of TDP-43 pathology was 19% (7/37). The frequency of TDP-43 pathology in diffuse neocortical type LBD-Ltau cases was 36% (4/11), which was higher than those in limbic and brain stem-predominant types (11-14%). The amygdala and entorhinal cortex were the most frequently affected sites of TDP-43 pathology in LBD-Ltau cases. In LBD-Ltau cases, the proportion of diffuse neocortical type LBD was higher in the TDP-43-positive cases, than that in TDP-43-negative cases (57 vs. 23%). In all LBD cases, α-synuclein pathology in the temporal cortex was significantly more severe in TDP-43-positive cases, and significantly correlated with the severity of TDP-43 pathology in the amygdala. In a multivariate model, the presence of severe α-synuclein pathology was significantly associated with the development of TDP-43 pathology independent of age at death and tau pathology. In the amygdala, TDP-43 was often colocalized with α-synuclein or tau. Given these findings, we suggest that α-synuclein pathology is associated with TDP-43 accumulation in LBD cases. More... »

PAGES

789-801

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00401-010-0731-9

    DOI

    http://dx.doi.org/10.1007/s00401-010-0731-9

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1049786965

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/20669025


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