University of Oulu

Solje, E.; Benussi, A.; Buratti, E.; Remes, A.M.; Haapasalo, A.; Borroni, B. State-of-the-Art Methods and Emerging Fluid Biomarkers in the Diagnostics of Dementia—A Short Review and Diagnostic Algorithm. Diagnostics 2021, 11, 788.

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

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Author: Solje, Eino1,2; Benussi, Alberto3; Buratti, Emanuele4;
Organizations: 1Institute of Clinical Medicine-Neurology, University of Eastern Finland, 70211 Kuopio, Finland
2Neuro Center, Neurology, Kuopio University Hospital, 70029 Kuopio, Finland
3Neurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, 25121 Brescia, Italy
4International Centre for Genetic Engineering and Biotechnology, 34149 Trieste, Italy
5Research Unit of Clinical Neuroscience, Neurology, University of Oulu, 90230 Oulu, Finland
6Medical Research Center (MRC), Oulu University Hospital, 90220 Oulu, Finland
7A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70211 Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.8 MB)
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Language: English
Published: Multidisciplinary Digital Publishing Institute, 2021
Publish Date: 2021-09-03


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.

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Series: Diagnostics
ISSN: 2075-4418
ISSN-E: 2075-4418
ISSN-L: 2075-4418
Volume: 11
Issue: 5
Article number: 788
DOI: 10.3390/diagnostics11050788
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3124 Neurology and psychiatry
3111 Biomedicine
Funding: This work was supported by Finnish Brain Foundation (E.S.), Orion Research Foundation (E.S.), Instrumentarium Science Foundation (E.S.), Sigrid Jusélius Foundation (E.S.), the Airalzh-AGYR2020 grant (A.B.), AriSLA grant PathensTDP (E.B.), The University of Oulu Scholarship Foundation (A.M.R.), Academy of Finland [grant numbers 315460 (A.M.R.), 315459 (A.H.)], and grant from Italian Ministry of Health (RF-2018-12366665) (B.B.).
Academy of Finland Grant Number: 315460
Detailed Information: 315460 (Academy of Finland Funding decision)
Copyright information: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (