Neuropathology, immunohistochemistry, and biochemistry in human prion diseases

Abstract

Human prion diseases are rare fatal neurodegenerative conditions that occur as sporadic, inherited, and acquired disorders. All are defined by characteristic neuropathological changes and by the accumulation of a disease-associated form of the prion protein in the brain. In variant CJD, prion protein also accumulates in lymphoid tissues and in the peripheral nervous system. Examination of the brain in human prion diseases is essential for a definite diagnosis and for disease surveillance. In this chapter we bring over 20 years’ experience of research and diagnosis in human prion diseases to provide detailed information on how to handle brain tissue from a case of human prion disease safely in a laboratory. We also describe how to make the diagnosis of a human prion disease using histological and biochemical techniques for the detection of disease-associated prion protein in the brain, and provide helpful notes for practical guidance and troubleshooting in the laboratory.