Prion diseases, a group of fatal
neurodegenerative disorders, are characterized by the presence of the abnormal
scrapie isoform of
prion protein (PrP(Sc)) in affected brains. A conformational change is believed to convert the normal cellular
prion protein into PrP(Sc). Detection of PrP(Sc) for diagnosis and prophylaxis is impaired because available Abs recognizing
epitopes on PrP fail to distinguish between PrP(Sc) and normal cellular
prion protein. Here, we report that an anti-
DNA Ab, OCD4, as well as gene 5
protein, a well established
DNA-binding protein, capture PrP from brains affected by
prion diseases in both humans and animals but not from unaffected controls. OCD4 appears to immunoreact with
DNA (or
a DNA-associated molecule) that forms a conformation-dependent complex with PrP in
prion diseases. Whereas PrP immunocaptured by OCD4 is largely
protease-resistant, a fraction of it remains
protease-sensitive. Moreover, OCD4 detects disease-associated PrP >10 times more efficiently than a widely used Ab to PrP. Our finding that anti-
DNA Abs and gene 5
protein specifically target disease-associated
DNA-PrP complexes in a wide variety of species and disease phenotypes opens new avenues in the study and diagnosis of
prion diseases.