Neuropathology 2000

Abstracts for Meetings

S06-2

Human Prion Diseases

Gambetti, P Case Western Reserve University, USA

When compared to other neurodegenerative diseases, human prion diseases are remarkable because they include 3 etiological forms (sporadic, inherited and acquired by infection), and have multiple and diverse pathological phenotypes. In addition to the three well-known major pathological patterns, Creutzfeldt-Jakob disease (CJD), fatal familial insomnia (FFI) and Gerstmann-Sträussler-Scheinker (GSS), there are patterns that are intermediate between CJD and GSS or lack distinctive features. Furthermore, each major form comprises a number of subtypes. Currently, the sporadic form of prion diseases includes five variants of CJD and the recently reported sporadic form of FFI. Several distinct new pathological phenotypes have been observed in the genetic form, while the form acquired by infection, includes at least four phenotypes. This variability is not random. Recent advances indicate that phenotypic heterogeneity in prion diseases is largely determined by the genotype at codon 129 which, in turn, affects the conformation of the scrapie prion protein. Evidence supporting similar a genotype-phenotype relationship mediated by the conformation of the amyloid precursor protein or its fragments has been recently uncovered in Alzheimer's disease. Supported by: NIH grants AG14359, AG08155, AG08012, CDC grant CCU 515004, the Britton Fund