title: Prion strain discrimination using luminescent conjugated polymers.
abstract: The occurrence of multiple strains of prions may reflect conformational variability of PrP(Sc), a disease-associated, aggregated variant of the cellular prion protein, PrP(C). Here we used luminescent conjugated polymers (LCPs), which emit conformation-dependent fluorescence spectra, for characterizing prion strains. LCP reactivity and emission spectra of brain sections discriminated among four immunohistochemically indistinguishable, serially mouse-passaged prion strains derived from sheep scrapie, chronic wasting disease (CWD), bovine spongiform encephalopathy (BSE), and mouse-adapted Rocky Mountain Laboratory scrapie prions. Furthermore, using LCPs we differentiated between field isolates of BSE and bovine amyloidotic spongiform encephalopathy, and identified noncongophilic deposits in prion-infected deer and sheep. We found that fibrils with distinct morphologies generated from chemically identical recombinant PrP yielded unique LCP spectra, suggesting that spectral characteristic differences resulted from distinct supramolecular PrP structures. LCPs may help to detect structural differences among discrete protein aggregates and to link protein conformational features with disease phenotypes.
authors.affiliation: UniversitätsSpital Zürich, Institute of Neuropathology, Department of Pathology, Schmelzbergstrasse 12, CH-8091 Zürich, Switzerland.
authors.forename: Christina J
authors.initials: CJ
authors.lastname: Sigurdson
authors.forename: K Peter R
authors.initials: KP
authors.lastname: Nilsson
authors.forename: Simone
authors.initials: S
authors.lastname: Hornemann
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Manco
authors.forename: Magdalini
authors.initials: M
authors.lastname: Polymenidou
authors.forename: Petra
authors.initials: P
authors.lastname: Schwarz
authors.forename: Mario
authors.initials: M
authors.lastname: Leclerc
authors.forename: Per
authors.initials: P
authors.lastname: Hammarström
authors.forename: Kurt
authors.initials: K
authors.lastname: Wüthrich
authors.forename: Adriano
authors.initials: A
authors.lastname: Aguzzi
mesh_terms: D000818:Animals; D003670:Deer; D020869:Gene Expression Profiling / Q000379:methods; D008163:Luminescent Measurements / Q000379:methods*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence / Q000379:methods*; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism*; D011108:Polymers / Q000737:chemistry; D017096:Prion Diseases / Q000378:metabolism*; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D046912:Multiprotein Complexes; D011108:Polymers; D011328:Prions