The authors report on a large series of human
prion diseases to establish ultrastructural characteristics that may be useful for their diagnosis. For
Creutzfeldt-Jakob disease (CJD and its variant, vCJD) and
fatal familial insomnia (FFI) only vacuolation (spongiform change) and the presence of tubulovesicular structures are consistent findings. Other changes, such as the presence of myelinated vacuoles, branching cisternae,
neuroaxonal dystrophy, and autophagic vacuoles, were present in different proportions in either CJD or FFI, but they are nonspecific ultrastructural findings that can also occur in other neurodegenerative conditions. The hallmark of Gerstmann-Sträussler-Scheinker disease (GSS) and vCJD is the
amyloid plaque, but plaques of GSS and
kuru are different than those of vCJD. Whereas the former are typical unicentric
kuru type or multicentric plaques, the latter are unicentric florid plaques. Also,
kuru plaques are nonneuritic, whereas GSS florid plaques are usually neuritic; however, a proportion of plaques from GSS was also found to have nonneuritic characteristics. Thus, the presence or absence of dystrophic neurites is not a discriminatory factor for GSS and vCJD. Furthermore, plaques from GSS with different mutations were also slightly different. In GSS with mutations P102L, 232T, and A117V plaques were stellate while in 1 case with 144 base-pair insertion and in GSS-A117V, round plaques were also observed, and typical primitive
neuritic plaques, i.e., composed of dystrophic neurites with little or no
amyloid, were found only in a P102L case from the original Austrian family. In 2 cases of
sporadic CJD, the
kuru stellate plaque predominated.