The use of Apolipoprotein B, Apolipoprotein E, fragments and mimetics thereof is provided for diagnostic, detection, prognostic and therapeutic applications In prion diseases. More specifically, the invention provides the use of Apolipoprotein B or fragments thereof for modulating or identifying modulators of the prion protein replication which are implicated in the pathogenesis of transmissible spongiform encephalopathics and other prion diseases.