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

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

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21 Citations (Scopus)

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 onTDP-43 accumulation, independent of tau pathology, we examined by immunohistochemistry 56 cases of LBD using a phosphorylationdependent 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 typeLBD-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 LBDLtau 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.

Original languageEnglish
Pages (from-to)789-801
Number of pages13
JournalActa neuropathologica
Volume120
Issue number6
DOIs
Publication statusPublished - Dec 2010
Externally publishedYes

Keywords

  • DLB
  • Lewy body disease
  • TDP-43
  • Tau
  • α-Synuclein

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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    Yokota, O., Davidson, Y., Arai, T., Hasegawa, M., Akiyama, H., Ishizu, H., Terada, S., Sikkink, S., Pickering-Brown, S., & Mann, D. M. A. (2010). Effect of topographical distribution of α-synuclein pathology on TDP-43 accumulation in Lewy body disease. Acta neuropathologica, 120(6), 789-801. https://doi.org/10.1007/s00401-010-0731-9