Tubulofilamentous particles and scrapie-associated fibrils (SAF) are ultrastructural markers, while protease-resistant protein (PrP) is a molecular biological marker for all spongiform encephalopathies. Review of all published work has suggested that PrP molecules aggregate to form a three-dimensional SAF. Further reports have suggested that a single-stranded DNA wraps round SAF and acquires an outer protein coat to form tubulofilamentous particles. As incubation period increases in the infected animals, larger amounts of PrP molecules are committed to form SAF, interfering with the normal supply of PrP to cell membranes which become disrupted and eventually fragment, resulting in vacuoles typical of those found in spongiform encephalopathies.