Recently we proposed that authentic prions responsible for lethal transmissible spongiform encephalopathies are comprised of infectious paired fibre PrP rods (20 nm in width, generating proteolytic fragments corresponding to PrP 27–30) [36] and that in IPD patient brain distinct single PrP fibres (approximately 10 nm in width that generate N- and C-terminally truncated protease-resistant fragments) may co-propagate and account for the abundant amyloid PrP plaques that distinguish the IPD neuropathological phenotype [37,38]. This evidence concerns the gene PRNP and human prion disease.