Contribution of CSF Biomarkers to the Early Diagnosis of Human Genetic Transmissible Spongiform Encephalopathies

Introduction

Human transmissible spongiform encephalopathies (TSEs) represent a group of neurodegenerative disorders, which, in contrast to a relatively short history is rich in surprising discoveries. The first unexpected finding was the transmissibility of the disease within and between mammalian species. The second was the glycoprotein “prion,” followed by the discovery of normal cellular prion protein (PrP), encoded in the prion protein gene (PRNP). The medical importance of TSEs is expressed less by their rare annual incidence (worldwide 0.5–1.5 per million) than by their unconventional biological properties, including their transmissibility, unique genetic control, and fatal prognosis.

Abstract

In this study, mainly the genetic forms of ‘Human transmissible spongiform encephalopathies’ (TSEs) are described. Subtypes of genetic TSEs, that is, genetic Creutzfeldt–Jakob disease, Gerstmann–Sträussler–Sheinker syndrome, and fatal familial insomnia are characterized. Available data on the penetrance of mutations of the prion protein gene are presented. The specific features of genetic TSEs, as anticipation and asymptomatic carriers of disease-specific mutations, are underlined. Attention was drawn to advantages of genetic TSEs concerning the early diagnosis, prevention, and prophylaxis. CSF biomarkers, used in the TSE diagnosis, are described. Implementation of assays detecting most frequently used brain-derived proteins in the CSF (protein 14-3-3, tau, S100b, neuron-specific enolase) and their usefulness alone or in combination for early diagnosis of genetic Creutzfeldt–Jakob disease is discussed.

Keywords

Genetic TSEs, CSF biomarkers, Early diagnosis