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Updated: Aug 21, 2026
Detection of Abnormal Prion Protein by Immunohistochemistry
Published on: May 5, 2023
Labeling of the scrapie-associated prion protein in vitro and in vivo
Valerie B Hoefert1, Judd M Aiken, Debbie McKenzie
1Department of Animal Health and Biomedical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison, 1656 Linden Drive, Madison, WI 53706, USA.
Abstract:
Prion diseases are a group of infectious neurodegenerative diseases that affect both animals and humans. A characteristic of prion diseases is the aggregation and accumulation of a disease-associated isoform of the prion protein in the brains of infected individuals. The amyloid imaging probe (trans,trans)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) has shown potential in the diagnosis of other amyloid disorders and we hypothesized that this compound would be effective in labeling prion protein plaques in vitro and in vivo. To test this, we compared BSB fluorescence to prion protein immunostaining on infected and uninfected brain tissue sections from scrapie-infected hamsters. We found that both methods labeled the same plaques in infected tissues while not substantially staining uninfected tissues. To test the potential of BSB as an in vivo label for prion aggregates, we perfused scrapie-infected animals with BSB and observed BSB labeled plaques co-stained with an anti-prion protein antibody. These results suggest that BSB may have use as a diagnostic tool for prion diseases. We were unable to detect BSB staining in preclinical scrapie-infected hamsters suggesting that the diagnostic potential of BSB could be limited in cases of prion disease that do not have plaques either due to a preclinical lack of pathology or disease agents like sporadic Creutzfeldt-Jakob disease (CJD), which generally lack prion plaques. However, BSB may be a useful for prion diseases where plaques are present, such as clinical variant CJD.
Insights
The amyloid imaging probe BSB effectively labels prion protein plaques in vitro and in vivo in animal models of prion disease. However, its diagnostic utility may be limited in preclinical stages or diseases lacking plaques, such as sporadic Creutzfeldt-Jakob disease.
Area of Science:
- Neuroscience
- Biochemistry
- Pathology
Background:
- Prion diseases are fatal neurodegenerative disorders characterized by abnormal prion protein aggregation in the brain.
- Existing diagnostic methods for prion diseases can be invasive or lack sensitivity in early stages.
- Amyloid imaging probes show promise for diagnosing other protein aggregation disorders.
Purpose of the Study:
- To evaluate the efficacy of the amyloid imaging probe (trans,trans)-1-bromo-2,5-bis-(3-hydroxycarbonyl-4-hydroxy)styrylbenzene (BSB) for labeling prion protein plaques.
- To assess the potential of BSB as an in vitro and in vivo diagnostic tool for prion diseases.
Main Methods:
- Comparison of BSB fluorescence with prion protein immunostaining on brain tissue sections from scrapie-infected and uninfected hamsters.
- In vivo perfusion of BSB in scrapie-infected animals followed by co-staining with an anti-prion protein antibody.
- Evaluation of BSB staining in preclinical and clinical stages of prion disease.
Main Results:
- BSB successfully labeled prion protein plaques in infected hamster brain tissues, colocalizing with immunostaining.
- In vivo studies showed BSB labeling of plaques in perfused scrapie-infected animals.
- BSB staining was not detected in preclinical scrapie-infected hamsters, indicating limitations in early-stage diagnosis.
Conclusions:
- BSB demonstrates potential as a diagnostic tool for prion diseases characterized by plaque formation.
- The diagnostic utility of BSB may be restricted to prion diseases with detectable plaques, such as clinical variant Creutzfeldt-Jakob disease.
- Further research is needed to explore BSB's application in preclinical prion disease diagnosis.
