Pathological spectrum of sporadic Creutzfeldt-Jakob disease.

Abstract

Human prion diseases are a rare group of transmissible neurodegenerative conditions which are classified according to their aetiology as sporadic, genetic or acquired forms. Creutzfeldt-Jakob disease (CJD) is the most common form of human prion disease, with the sporadic form accounting for ∼85% of all reported cases. While advances have been made in the development of clinical tools and biomarkers in the diagnosis of prion disease, allowing greater diagnostic certainty for surveillance purposes, definitive diagnosis requires neuropathological examination of the brain at postmortem. Since the 1990s, efforts have been made to develop a classification system for sporadic CJD (sCJD) based on observed differences in the clinical features and the pathological phenotype (the nature and degree of spongiform vacuolation, neuronal loss, astrogliosis and misfolded prion protein accumulation in the brain), also referred to as the 'histotype'. Six major clinicopathological subtypes of sCJD are internationally recognised, largely correlating with the combination of the two distinct types of the protease-resistant prion protein (PrP^res type 1 or 2) and the methionine (M)/valine (V) polymorphism at codon 129 of the prion protein gene (PRNP): MM1/MV1, MM2-cortical, MM2-thalamic, MV2, VV1 and VV2. This classification system has been extended to recognise sCJD cases demonstrating both mixed PrP^res types or mixed histotypes in the brain of the same individual, as well as including atypical or novel pathological phenotypes. In this review, we will provide an up-to-date overview of the current classification of sCJD based on the prominent neuropathological features. In addition, with levels of infectivity at their highest in the brain, we will also discuss the additional precautions that are recommended when handling and examining postmortem tissues from patients with suspected prion disease.