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Chalatsa et al. Neuroimmunol Neuroinflammation 2020;7:132-40 Neuroimmunology
DOI: 10.20517/2347-8659.2020.01 and Neuroinflammation

Review Open Access

Assessment of cerebrospinal fluid α-synuclein as
a potential biomarker in Parkinson’s disease and

synucleinopathies

Ioanna Chalatsa , Katerina Melachroinou , Evangelia Emmanouilidou , Kostas Vekrellis 1
1,2
1
1
1 Center for Basic Science, Biomedical Research Foundation Academy of Athens, Athens 11527, Greece.
2 Laboratory of Biochemistry, Department of Chemistry, National and Kapodistrian University of Athens, Athens 11527, Greece.
Correspondence to: Dr. Kostas Vekrellis, Center for Basic Science, Biomedical Research Foundation Academy of Athens, 4
Soranou Ephessiou St., Athens 11527, Greece. E-mail: vekrellis@bioacademy.gr

How to cite this article: Chalatsa I, Melachroinou K, Emmanouilidou E, Vekrellis K. Assessment of cerebrospinal fluid α-synuclein
as a potential biomarker in Parkinson’s disease and synucleinopathies. Neuroimmunol Neuroinflammation 2020;7:132-40.
http://dx.doi.org/10.20517/2347-8659.2020.01

Received: 2 Jan 2020 First Decision: 10 Mar 2020 Revised: 23 Mar 2020 Accepted: 7 Apr 2020 Available online: 16 May 2020

Science Editor: George P. Paraskevas Copy Editor: Jing-Wen Zhang Production Editor: Jing Yu

Abstract
The discovery of diagnostic and prognostic biomarkers for neurodegenerative diseases represents an unmet
clinical challenge. For example, the diagnosis of Parkinson’s disease (PD) relies mainly on the presence of clinical
symptoms. Therefore, the identification and use of novel PD biomarkers would allow the application of disease-
modifying treatments at the very early stages of neurodegeneration. The presynaptic protein, α-synuclein, has
been genetically and biochemically linked with PD pathogenesis and has been considered as a potential biomarker
for the diagnosis of PD and the related synucleinopathies. The vast majority of studies have assessed the
measurement of α-synuclein, alone or in combination with other biomarkers in the cerebrospinal fluid (CSF), since
it is the biofluid that most closely reflects the pathophysiology of the brain. The diagnostic value of the monomeric
α-synuclein but also the oligomeric, the phosphorylated and the aggregated forms of the protein has been
evaluated using a variety of immunoassays. The results have so far been reproducible but the assays used are still
lacking the required diagnostic accuracy. Recent reports have shown that Protein misfolding cyclic amplification is
a technique that has the potential to detect α-synuclein seeds in samples of CSF with high sensitivity and across
different synucleinopathies. In an effort to increase the source of biomarker for PD and related synucleinopathies,
α-synuclein has also been measured in neuronal exosomes, small vesicles of endosomal origin that are secreted
from neurons into the CSF or the periphery. The potential diagnostic value of exosomes stems from the notion
that exosomes carry a disease-specific repertoire of marker proteins. Therefore, the assessment of exosome-
associated α-synuclein species may also open up new avenues for disease diagnosis in different synucleinopathies.

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license,
and indicate if changes were made.

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