PrPSc deposits in mice injected with Y226X brain were found mainly in pons, thalamus and midbrain. Deposits varied in character from large plaque-like deposits to coarse or medium deposits in perineuronal sites or neuropil (Fig. 2 and Table 2). In different mice deposits in the same region, i.e. pons, were sometimes different (Fig. 2a versus 2b). Interestingly, no mice had perivascular PrPSc which were very common sites in the original human patient. Thioflavin S staining for amyloid showed that some, but not all, of the large plaque-like deposits in tg66 mice were positive (Fig. 2, panel a-2, insert). This was markedly different from the pattern of perivascular amyloid and CAA seen previously in scrapie-infected tg44 mice expressing truncated anchorless PrP [8, 36, 39]. Thus, the formation of abundant PrPSc amyloid in the Y226X patient appeared to be dependent on the synthesis of anchorless PrP in this patient. In contrast, amyloid PrPSc was minimal in the tg66 mice in the present transmission experiments apparently due to the low amount of anchorless PrP made by these recipient mice.