Dipeptide repeat proteins are present in the p62 positive inclusions in patients with frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72Report as inadecuate




Dipeptide repeat proteins are present in the p62 positive inclusions in patients with frontotemporal lobar degeneration and motor neurone disease associated with expansions in C9ORF72 - Download this document for free, or read online. Document in PDF available to download.

Acta Neuropathologica Communications

, 1:68

First Online: 14 October 2013Received: 23 September 2013Accepted: 07 October 2013

Abstract

BackgroundCases of Frontotemporal Lobar Degeneration FTLD and Motor Neurone Disease MND associated with expansions in C9ORF72 gene are characterised pathologically by the presence of TDP-43 negative, but p62 positive, inclusions in granule cells of the cerebellum and in cells of dentate gyrus and area CA4 of the hippocampus.

ResultsWe screened 84 cases of pathologically confirmed FTLD and 23 cases of MND for the presence of p62 positive inclusions in these three brain regions, and identified 13 positive cases of FTLD and 3 of MND. All cases demonstrated expansions in C9ORF72 by Southern blotting where frozen tissues were available. The p62 positive inclusions in both cerebellum and hippocampus were immunostained by antibodies to dipeptide repeat proteins DPR, poly Gly-Ala poly-GA, poly Gly-Pro poly-GP and poly Gly-Arg poly-GR, these arising from a putative non-ATG initiated RAN sense translation of the GGGGCC expansion. There was also some slight, but variable, immunostaining with poly-AP antibody implying some antisense translation might also occur, though the relative paucity of immunostaining could reflect poor antigen avidity on the part of the antisense antibodies. Of the FTLD cases with DPR, 6 showed TDP-43 type A and 6 had TDP-43 type B histology; one had FTLD-tau with the pathology of corticobasal degeneration. There were no qualitative or quantitative differences in the pattern of immunostaining with antibodies to DPR, or p62, proteins between TDP-43 type A and type B cases. Ratings for frequency of inclusions immunostained by these poly-GA, poly-GP and poly-GR antibodies broadly correlated with those for immunolabelled by p62 antibody in all three regions.

ConclusionWe conclude that DPR are a major component of p62 positive inclusions in FTLD and MND.

KeywordsFrontotemporal lobar degeneration C9ORF72 p62 inclusions Dipeptide repeat proteins Electronic supplementary materialThe online version of this article doi:10.1186-2051-5960-1-68 contains supplementary material, which is available to authorized users.

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Author: David MA Mann - Sara Rollinson - Andrew Robinson - Janis Bennion Callister - Jennifer C Thompson - Julie S Snowden - Tani

Source: https://link.springer.com/



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