The use of Apolipoprotein B, Apoliporpotein E, fragments and mimetics thereofis provided for diagnostic, detection, prognostic and therapeutic applicationsin prion diseases. More specifically, the invention provides the use ofApolipoprotein B or fragments thereof for modulating or identifying modulatorsof the prion protein replication which are implicated in thepathogenesis oftransmissible spongiform encephalopathics and other prion diseases.