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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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

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Synucleins
Lewy Body Disease
Pathology
Amygdala
Entorhinal Cortex

Keywords

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

ASJC Scopus subject areas

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

Cite this

Yokota, O., Davidson, Y., Arai, T., Hasegawa, M., Akiyama, H., Ishizu, H., ... 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

Effect of topographical distribution of α-synuclein pathology on TDP-43 accumulation in Lewy body disease. / Yokota, Osamu; Davidson, Yvonne; Arai, Tetsuaki; Hasegawa, Masato; Akiyama, Haruhiko; Ishizu, Hideki; Terada, Seishi; Sikkink, Stephen; Pickering-Brown, Stuart; Mann, David M A.

In: Acta Neuropathologica, Vol. 120, No. 6, 12.2010, p. 789-801.

Research output: Contribution to journalArticle

Yokota, O, Davidson, Y, Arai, T, Hasegawa, M, Akiyama, H, Ishizu, H, Terada, S, Sikkink, S, Pickering-Brown, S & Mann, DMA 2010, 'Effect of topographical distribution of α-synuclein pathology on TDP-43 accumulation in Lewy body disease', Acta Neuropathologica, vol. 120, no. 6, pp. 789-801. https://doi.org/10.1007/s00401-010-0731-9
Yokota, Osamu ; Davidson, Yvonne ; Arai, Tetsuaki ; Hasegawa, Masato ; Akiyama, Haruhiko ; Ishizu, Hideki ; Terada, Seishi ; Sikkink, Stephen ; Pickering-Brown, Stuart ; Mann, David M A. / Effect of topographical distribution of α-synuclein pathology on TDP-43 accumulation in Lewy body disease. In: Acta Neuropathologica. 2010 ; Vol. 120, No. 6. pp. 789-801.
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