State-of-the-art methods and emerging fluid biomarkers in the diagnostics of dementia—a short review and diagnostic algorithm

The most common neurodegenerative dementias include Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). The correct etiology-based diagnosis is pivotal for clinical management of these diseases as well as for the suitable timing and choosing the accurate disease-modifying therapies when these become available. Enzyme-linked immunosorbent assay (ELISA)-based methods, detecting altered levels of cerebrospinal fluid (CSF) Tau, phosphorylated Tau, and Aβ-42 in AD, allowed the wide use of this set of biomarkers in clinical practice. These analyses demonstrate a high diagnostic accuracy in AD but suffer from a relatively restricted usefulness due to invasiveness and lack of prognostic value. In recent years, the development of novel advanced techniques has offered new state-of-the-art opportunities in biomarker discovery. These include single molecule array technology (SIMOA), a tool for non-invasive analysis of ultra-low levels of central nervous system-derived molecules from biofluids, such as CSF or blood, and real-time quaking (RT-QuIC), developed to analyze misfolded proteins. In the present review, we describe the history of methods used in the fluid biomarker analyses of dementia, discuss specific emerging biomarkers with translational potential for clinical use, and suggest an algorithm for the use of new non-invasive blood biomarkers in clinical practice.