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

Acta Neuropathol 2010 Dec 29;120(6):789-801. Epub 2010 Jul 29.

Greater Manchester Neurosciences Centre, Hope Hospital, University of Manchester, Salford, UK.

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.

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December 2010
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References

(Supplied by CrossRef)

C Amador-Ortiz et al.
Ann Neurol 2007

T Arai et al.
Acta Neuropathol 2009

T Arai et al.
Biochem Biophys Res Commun 2006

H Braak et al.
Acta Neuropathol 2006

NJ Cairns et al.
Am J Pathol 2007

NJ Cairns et al.
Acta Neuropathol 2007

Y Davidson et al.
Acta Neuropathol 2007

H Fujishiro et al.
Acta Neuropathol 2009

F Geser et al.
Acta Neuropathol 2008

F Geser et al.
J Neurol 2009

L Hansen et al.
Neurology 1990

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