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Diagnosis of Prion Disease: Conventional Approaches

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Prions and Diseases

Abstract

Prion diseases are characterized by the deposition of PrPSc, an abnormal form of the normal cellular protein, PrPc in the brain. The unique nature of human prion diseases includes their pathogenesis, mode of transmission, and neuropathology. In humans, a long incubation time, rapid and dramatic evolution of the disease course, and always a lethal outcome are key features of the clinical syndrome. The clinical diagnosis in sCJD is supported by detection of periodic sharp and slow wave complexes (PSWCs) in the electroencephalogram, 14-3-3 proteins, the detection of the abnormal PrP of in the cerebrospinal fluid (CSF) via RT-QuIC, and hyperintense signal changes in the basal ganglia, thalamus and cortical areas on magnetic resonance imaging (MRI). These tests became part of the clinical diagnostic criteria for CJD. Elevated levels of brain-derived proteins in plasma such as neurofilaments or tau might contribute to the clinical diagnosis in the future. The sensitivity of diagnostic tests varies across molecular CJD subtypes. Alzheimer’s disease and Lewy body dementia are the most frequent differential diagnoses in elderly patients, while chronic inflammatory CNS disorders and autoimmune mediated encephalitis have to be considered in younger patients.

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Zerr, I., Hermann, P. (2023). Diagnosis of Prion Disease: Conventional Approaches. In: Zou, WQ., Gambetti, P. (eds) Prions and Diseases. Springer, Cham. https://doi.org/10.1007/978-3-031-20565-1_33

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