Neuropathological Diagnosis of Human Prion Disease: Morphological Studies

The neuropathology of the classical human prion diseases, Creutzfeldt-Jakob dtsease (CJD), Gerstmann-Straussler-Scheinker syndrome (GSS), and kuru, is characterized by four main featureundefined spongiform change, neuronal loss, ghiosts, and amyloid plaque formation (1 –3 . These features are shared with prion diseases in animals; the recognition of these similarities prompted the first attempts to transmit a human priori disease (kuru) to a primate in 1966 (4 , followed by CJD in 1968 (5 ) and GSS in 1981 (6 ). These neuropathological features have formed the basis of the morphological diagnosts of human prion diseases for many years, although it was recognized that these changes are enormously variable both from case to case and within the central nervous system (CNS) in individual cases (7 ). In this respect, it is interesting to note that the original case reported by Creutzfeldt (8 , 9 ) and two of the original cases reported by Jakob (10 –12 ) do not show any of these characteristic neuropathological features; the diagnosis in these cases remains uncertain on review (7 , 13 ). However, at least two of Jakob’s original cases show typical neuropathological changes and other cases subsequently reported from his laboratory (including the members of the Backer family) also exhibited classical histological features (12 , 14 ). It is also of interest to note that prion protein (PrP) gene analysis has recently been performed on one of the Backer family cases, showing a codon 178 Asn mutation with met/val at codon 129 (15 . This genotype has been described in other familial forms of human prion disease (16 (see Chapter 2).