Localization of A11-reactive oligomeric species in prion diseases

TY - JOUR

T1 - Localization of A11-reactive oligomeric species in prion diseases

AU - Aidt, Frederik H

AU - Hasholt, Lis F

AU - Christiansen, Michael

AU - Laursen, Henning

N1 - © 2013 Blackwell Publishing Ltd.

PY - 2013/6

Y1 - 2013/6

N2 - 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 (PrpSc). 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 PrpSc overlaps. We argue that the A11-reactive species are indeed composed of oligomeric PrpSc, and suggest that the toxic effects of PrpSc oligomers could be related to the generic oligomeric conformation recognized by A11.

AB - 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 (PrpSc). 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 PrpSc overlaps. We argue that the A11-reactive species are indeed composed of oligomeric PrpSc, and suggest that the toxic effects of PrpSc oligomers could be related to the generic oligomeric conformation recognized by A11.

U2 - 10.1111/his.12097

DO - 10.1111/his.12097

M3 - Journal article

C2 - 23570304

SN - 0309-0167

VL - 62

SP - 994

EP - 1001

JO - Histopathology

JF - Histopathology

IS - 7

ER -