APOE and scrapie: Therefore, we examined the effect of APOE polymorphism on prion pathology using APOE-TR mice we infected with 22L mouse adapted scrapie strain and while we found no effect of the APOE genotype on extra-CNS PrPSc accumulation and neuroinvasion, the ensuing brain pathology was significantly intensified in the presence of the ε4 allele and to lesser extent in the presence of the ε2 allele.