Abstract
Prion diseases, synucleinopathies and tauopathies are neurodegenerative disorders characterized by deposition of abnormal protein aggregates in brain and other tissues. These aggregates consist of misfolded forms of prion, α-synuclein (αSyn), or tau proteins that cause neurodegeneration and represent hallmarks of these disorders. A main challenge in the management of these diseases is the accurate detection and differentiation of these abnormal proteins during the early stages of disease before the onset of severe clinical symptoms. Unfortunately, many clinical manifestations may occur only after neuronal damage is already advanced and definite diagnoses typically require post-mortem neuropathological analysis. Over the last decade, several methods have been developed to increase the sensitivity of prion detection with the aim of finding reliable assays for the accurate diagnosis of prion disorders. Among these, the real-time quaking-induced conversion (RT–QuIC) assay now provides a validated diagnostic tool for human patients, with positive results being accepted as an official criterion for a diagnosis of probable prion disease in multiple countries. In recent years, applications of this approach to the diagnosis of other prion-like disorders, such as synucleinopathies and tauopathies, have been developed. In this review, we summarize the current knowledge on the use of the RT-QuIC assays for human proteopathies.
Highlights
Several neurodegenerative proteinopathies are characterized by the conformational change of specific native proteins, which form intra- or extracellular pathological aggregates in particular brain regions, leading to neurodegeneration and progression of clinical symptoms
We summarize recent advances in the application of real-time quaking- induced conversion (RT-QuIC) assays to the study and diagnosis of these human proteopathies
RT-QuIC assays have been adapted by many laboratories to a wide range of biospecimens [e.g., brain homogenates (BH), cerebrospinal fluid (CSF), plasma, olfactory mucosa (OM), skin] and prions, from the most common sCJD to rare genetic forms in humans
Summary
Several neurodegenerative proteinopathies are characterized by the conformational change of specific native proteins, which form intra- or extracellular pathological aggregates in particular brain regions, leading to neurodegeneration and progression of clinical symptoms. The proteins involved and the resultant clinical symptoms vary, these proteopathies share a common prion-like seeded propagation mechanism for the causative aggregates. These aggregates may be present in biological fluids and tissues prior to the onset of clinical signs, making them attractive biomarkers for the early diagnosis of the associated neurodegenerative disorders. Their detection can be challenging due to low concentrations in accessible biospecimens. We summarize recent advances in the application of RT-QuIC assays to the study and diagnosis of these human proteopathies
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