Proteopathic seed amplification assays in easily accessible specimens for human synucleinopathies, tauopathies, and prionopathies: A scoping review

Abstract

A hallmark event in neurodegenerative diseases is represented by the misfolding, aggregation and accumulation of proteins, leading to cellular and network dysfunction preceding the development of clinical symptoms by years. Early diagnosis represents a crucial issue in the field of neuroscience as it offers the potential to utilize this therapeutic window in the future to manage disease-modifying therapy. Seed amplification assays, including Real-Time Quaking-Induced Conversion (RT-QuIC) and Protein Misfolding Cyclic Amplification (PMCA), have emerged in recent years as innovative techniques developed to detect minute amounts of amyloidogenic proteins. These techniques can utilize various biological fluids and tissues, with most evidence to date regarding their potential diagnostic use focusing on cerebrospinal fluid. In this scoping review, we aimed to investigate and discuss the available evidence regarding the diagnostic use of these assays on easily accessible biological fluids and tissues in patients affected by synucleinopathies, tauopathies or prion diseases. From a systematic search on two databases, Scopus and Pubmed, we identified 49 studies. Although most identified studies have used skin and olfactory mucosa as biological samples, there is preliminary evidence suggesting the potential implementation of these techniques using fluids as blood, saliva and tears. The results achieved so far, as well as methodological aspects and limitations to overcome, are discussed.