Prion disease
Akın Nihat, Tzehow Mok, John Collinge
Abstract
Abstract Prion diseases are fatal neurodegenerative conditions that may arise sporadically or be inherited or acquired by environmental exposure to infectious prions—transmissible agents composed of multimeric assemblies of misfolded protein. The core clinical features are progressive cognitive decline, accompanied with ataxia, myoclonus, and pyramidal or extra-pramidal motor signs. While the most common form—sporadic Creutzfeldt–Jakob disease—is generally rapidly progressive over weeks or months, inherited prion diseases can span many years, with diverse clinical features readily mimicking other neurodegenerative diseases. Psychiatric features, including agitation, anxiety, depression, hallucinations, and behavioural disturbances, are common in the early stages. Diagnosis can usually be made with confidence by the combination of clinical criteria, diffusion-weighted magnetic resonance imaging, electroencephalogram, and specialized cerebrospinal fluid analysis. Inherited prion disease can be confirmed with prion protein gene analysis, which should be considered in all early-onset dementing and ataxic conditions. It is now becoming clear that the fundamental molecular pathogenesis—seeded protein polymerization—is relevant to other neurodegenerative diseases, notably Alzheimer’s disease.