skip to main content
Language:
Search Limited to: Search Limited to: Resource type Show Results with: Show Results with: Index

Dipeptide repeat protein toxicity in frontotemporal lobar degeneration and in motor neurone disease associated with expansions in C9ORF72—a cautionary note

Mann, David M.A.

Neurobiology of Aging, February 2015, Vol.36(2), pp.1224-1226 [Peer Reviewed Journal]

Full text available

View all versions
Citations Cited by
  • Title:
    Dipeptide repeat protein toxicity in frontotemporal lobar degeneration and in motor neurone disease associated with expansions in C9ORF72—a cautionary note
  • Author: Mann, David M.A.
  • Description: Background Cases 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. Results We 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. Conclusion We conclude that DPR are a major component of p62 positive inclusions in FTLD and MND. Keywords: Frontotemporal lobar degeneration, C9ORF72, p62 inclusions, Dipeptide repeat proteins
  • Is Part Of: Neurobiology of Aging, February 2015, Vol.36(2), pp.1224-1226
  • Identifier: ISSN: 0197-4580 ; DOI: 10.1016/j.neurobiolaging.2014.10.011
  • Subjects: Nervous System Diseases -- Genetic Aspects ; Proteins ; Glycine ; Antibodies ; Gene Mutation
  • Language: English

Searching Remote Databases, Please Wait