Localization of A11‐reactive oligomeric species in prion diseases. Issue 7 (9th April 2013)

• Record Type: Journal Article
• Authors: Aidt, Frederik H; Hasholt, Lis F; Christiansen, Michael; Laursen, Henning
• Is Part Of: Histopathology. Volume 62:Issue 7(2013)
• Page Start: 994
• Page End: 1001
• Publication Date: 2013-04-09
• Subjects: A11 -- amyloid -- Creutzfeldt–Jakob disease -- immunohistochemistry -- neurodegeneration -- prion diseases -- PrpSc proteins; Histology, Pathological -- Periodicals; 611.018
• DOI: 10.1111/his.12097
• Languages: English
• ISSNs: 0309-0167

Abstract

Abstract : Aims: To investigate in prion diseases the in‐situ localization of prion protein oligomers sharing a common epitope with amyloid oligomers involved in a range of neurodegenerative diseases. Methods and results: We performed immunohistochemistry on sporadic Creutzfeldt–Jakob disease (sCJD) ( n = 9) and hereditary Gerstmann–Sträussler–Scheinker disease (GSS) ( n = 1) specimens with the anti‐oligomer antibody A11 to determine the localization of reactive species. We found that A11 reactivity in the sCJD specimens was localized to the cerebral and cerebellar cortices both in spongiform and adjacent, non‐spongiform areas, reminiscent of multicentric or diffuse plaques. In the GSS specimens, we found that staining was closely associated with kuru‐like plaques, and that A11‐reactive species colocalized with protease‐resistant prion protein (Prp Sc ). We also observed sporadic neuronal cytosolic staining in both types of specimen. Conclusions: We confirm that intracellular and extracellular A11‐reactive species are present in situ in sCJD cases and GSS, and that immunoreactivity for A11 and Prp Sc overlaps. We argue that the A11‐reactive species are indeed composed of oligomeric Prp Sc, and suggest that the toxic effects of Prp Sc oligomers could be related to the generic oligomeric conformation recognized by A11.