Cerebrospinal Fluid and Blood Exosomes As Biomarkers for Amyotrophic Lateral Sclerosis; a Systematic Review

Overview

Journal Diagn Pathol

Publisher Biomed Central

Specialty Pathology

Date 2024 Mar 1

PMID 38429818

Authors

Shahram Darabi

Armin Ariaei

Auob Rustamzadeh

Dariush Afshari

Enam Alhagh Charkhat Gorgich

Leila Darabi

Affiliations

Soon will be listed here.

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal motor neuron disease. Due to the limited knowledge about potential biomarkers that help in early diagnosis and monitoring disease progression, today's diagnoses are based on ruling out other diseases, neurography, and electromyography examination, which takes a time-consuming procedure.

Methods: PubMed, ScienceDirect, and Web of Science were explored to extract articles published from January 2015 to June 2023. In the searching strategy following keywords were included; amyotrophic lateral sclerosis, biomarkers, cerebrospinal fluid, serum, and plama.

Results: A total number of 6 studies describing fluid-based exosomal biomarkers were included in this study. Aggregated proteins including SOD1, TDP-43, pTDP-43, and FUS could be detected in the microvesicles (MVs). Moreover, TDP-43 and NFL extracted from plasma exosomes could be used as prognostic biomarkers. Also, downregulated miR-27a-3p detected through exoEasy Maxi and exoQuick Kit in the plasma could be measured as a diagnostic biomarker. Eventually, the upregulated level of CORO1A could be used to monitor disease progression.

Conclusion: Based on the results, each biomarker alone is insufficient to evaluate ALS. CNS-derived exosomes contain multiple ALS-related biomarkers (SOD1, TDP-43, pTDP-43, FUS, and miRNAs) that are detectable in cerebrospinal fluid and blood is a proper alternation. Exosome detecting kits listed as exoEasy, ExoQuick, Exo-spin, ME kit, ExoQuick Plus, and Exo-Flow, are helpful to reach this purpose.

Citing Articles

Metabolomic and Proteomic Profiling of Serum-Derived Extracellular Vesicles from Early-Stage Amyotrophic Lateral Sclerosis Patients.

Al Ojaimi Y, Vallet N, Dangoumau A, Lanznaster D, Bruno C, Lefevre A J Mol Neurosci. 2025; 75(1):21.

PMID: 39954028 DOI: 10.1007/s12031-025-02315-w.

References

Yelick J, Men Y, Jin S, Seo S, Espejo-Porras F, Yang Y . Elevated exosomal secretion of miR-124-3p from spinal neurons positively associates with disease severity in ALS. Exp Neurol. 2020; 333:113414. PMC: 7502520. DOI: 10.1016/j.expneurol.2020.113414. View

Siedler D, Chuah M, Kirkcaldie M, Vickers J, King A . Diffuse axonal injury in brain trauma: insights from alterations in neurofilaments. Front Cell Neurosci. 2015; 8:429. PMC: 4269130. DOI: 10.3389/fncel.2014.00429. View

Macias M, Rebmann V, Mateos B, Varo N, Perez-Gracia J, Alegre E . Comparison of six commercial serum exosome isolation methods suitable for clinical laboratories. Effect in cytokine analysis. Clin Chem Lab Med. 2019; 57(10):1539-1545. DOI: 10.1515/cclm-2018-1297. View

Vejux A, Namsi A, Nury T, Moreau T, Lizard G . Biomarkers of Amyotrophic Lateral Sclerosis: Current Status and Interest of Oxysterols and Phytosterols. Front Mol Neurosci. 2018; 11:12. PMC: 5797798. DOI: 10.3389/fnmol.2018.00012. View

Bonafede R, Mariotti R . ALS Pathogenesis and Therapeutic Approaches: The Role of Mesenchymal Stem Cells and Extracellular Vesicles. Front Cell Neurosci. 2017; 11:80. PMC: 5359305. DOI: 10.3389/fncel.2017.00080. View

Feneberg E, Steinacker P, Volk A, Weishaupt J, Wollmer M, Boxer A . Progranulin as a candidate biomarker for therapeutic trial in patients with ALS and FTLD. J Neural Transm (Vienna). 2015; 123(3):289-96. DOI: 10.1007/s00702-015-1486-1. View

Dolinar A, Koritnik B, Glavac D, Ravnik-Glavac M . Circular RNAs as Potential Blood Biomarkers in Amyotrophic Lateral Sclerosis. Mol Neurobiol. 2019; 56(12):8052-8062. PMC: 6834740. DOI: 10.1007/s12035-019-1627-x. View

Rotunno M, Bosco D . An emerging role for misfolded wild-type SOD1 in sporadic ALS pathogenesis. Front Cell Neurosci. 2014; 7:253. PMC: 3863749. DOI: 10.3389/fncel.2013.00253. View

Aydemir D, Ulusu N . Importance of the serum biochemical parameters as potential biomarkers for rapid diagnosis and evaluating preclinical stage of ALS. Med Hypotheses. 2020; 141:109736. DOI: 10.1016/j.mehy.2020.109736. View

10.

Kocar T, Muller H, Ludolph A, Kassubek J . Feature selection from magnetic resonance imaging data in ALS: a systematic review. Ther Adv Chronic Dis. 2021; 12:20406223211051002. PMC: 8521429. DOI: 10.1177/20406223211051002. View

11.

Walhout R, Verstraete E, van den Heuvel M, Veldink J, van den Berg L . Patterns of symptom development in patients with motor neuron disease. Amyotroph Lateral Scler Frontotemporal Degener. 2017; 19(1-2):21-28. DOI: 10.1080/21678421.2017.1386688. View

12.

Sibilla C, Bertolotti A . Prion Properties of SOD1 in Amyotrophic Lateral Sclerosis and Potential Therapy. Cold Spring Harb Perspect Biol. 2017; 9(10). PMC: 5630002. DOI: 10.1101/cshperspect.a024141. View

13.

Schreiber S, Debska-Vielhaber G, Abdulla S, Machts J, Schreiber F, Kropf S . Peripheral nerve atrophy together with higher cerebrospinal fluid progranulin indicate axonal damage in amyotrophic lateral sclerosis. Muscle Nerve. 2017; 57(2):273-278. DOI: 10.1002/mus.25682. View

14.

Westergard T, Jensen B, Wen X, Cai J, Kropf E, Iacovitti L . Cell-to-Cell Transmission of Dipeptide Repeat Proteins Linked to C9orf72-ALS/FTD. Cell Rep. 2016; 17(3):645-652. PMC: 5078984. DOI: 10.1016/j.celrep.2016.09.032. View

15.

Di Paola M, Di Iulio F, Cherubini A, Blundo C, Casini A, Sancesario G . When, where, and how the corpus callosum changes in MCI and AD: a multimodal MRI study. Neurology. 2010; 74(14):1136-42. DOI: 10.1212/WNL.0b013e3181d7d8cb. View

16.

Sun J, Carrero J, Zagai U, Evans M, Ingre C, Pawitan Y . Blood biomarkers and prognosis of amyotrophic lateral sclerosis. Eur J Neurol. 2020; 27(11):2125-2133. DOI: 10.1111/ene.14409. View

17.

De Felice B, Guida M, Guida M, Coppola C, De Mieri G, Cotrufo R . A miRNA signature in leukocytes from sporadic amyotrophic lateral sclerosis. Gene. 2012; 508(1):35-40. DOI: 10.1016/j.gene.2012.07.058. View

18.

Furtner J, Genbrugge E, Gorlia T, Bendszus M, Nowosielski M, Golfinopoulos V . Temporal muscle thickness is an independent prognostic marker in patients with progressive glioblastoma: translational imaging analysis of the EORTC 26101 trial. Neuro Oncol. 2019; 21(12):1587-1594. PMC: 6917403. DOI: 10.1093/neuonc/noz131. View

19.

Halbgebauer S, Steinacker P, Verde F, Weishaupt J, Oeckl P, von Arnim C . Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS. J Neurol Neurosurg Psychiatry. 2021; 93(1):68-74. DOI: 10.1136/jnnp-2021-327129. View

20.

Vu L, Bowser R . Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis. Neurotherapeutics. 2016; 14(1):119-134. PMC: 5233638. DOI: 10.1007/s13311-016-0503-x. View