Chapter 9 - Sporadic Creutzfeldt–Jakob disease

Abstract

Sporadic Creutzfeldt-Jakob disease (CJD), the most common human prion disease, is generally regarded as a spontaneous neurodegenerative illness, arising either from a spontaneous PRNP somatic mutation or a stochastic PrP structural change. Alternatively, the possibility of an infection from animals or other source remains to be completely ruled out. Sporadic CJD is clinically characterized by rapidly progressive dementia with ataxia, myoclonus, or other neurologic signs and, neuropathologically, by the presence of aggregates of abnormal prion protein, spongiform change, neuronal loss, and gliosis. Despite these common features the disease shows a wide phenotypic variability which was recognized since its early descriptions. In the late 1990s the identification of key molecular determinants of phenotypic expression and the availability of a large series of neuropathologically verified cases led to the characterization of definite clinicopathologic and molecular disease subtypes and to an internationally recognized disease classification. By showing that these disease subtypes correspond to specific agent strain-host genotype combinations, recent transmission studies have confirmed the biologic basis of this classification. The introduction of brain magnetic resonance imaging techniques such as fluid-attenuated inversion recovery and diffusion-weighted imaging sequences and cerebrospinal fluid biomarker assays for the detection of brain-derived proteins as well as real-time quaking-induced conversion assay, allowing the specific detection of prions in accessible biologic fluids and tissues, has significantly contributed to the improved accuracy of the clinical diagnosis of sporadic CJD in recent years.