A New Diagnostic Tool for Brain Disorders: Extracellular Vesicles Derived from Neuron, Astrocyte, and Oligodendrocyte

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2023 Aug 25

PMID 37621405

Authors

Xueying Wang

Huihui Yang

Chunyu Liu

Kefu Liu

Affiliations

Soon will be listed here.

Abstract

Brain disorders are the leading cause of disability worldwide, affecting people's quality of life and causing economic burdens. The current clinical diagnosis of brain disorders relies solely on individual phenotypes and lacks accurate molecular biomarkers. An emerging field of research centers around extracellular vesicles (EVs), nanoscale membrane vesicles which can easily cross the blood-brain barrier. EVs in the blood are derived from various tissues, including the brain. Therefore, purifying central nervous system (CNS)-derived EVs from the blood and analyzing their contents may be a relatively non-invasive way to analyze brain molecular alterations and identify biomarkers in brain disorders. Recently, methods for capturing neuron-derived EVs (NDEs), astrocyte-derived EVs (ADEs), and oligodendrocyte-derived EVs (ODEs) in peripheral blood were reported. In this article, we provide an overview of the research history of EVs in the blood, specifically focusing on biomarker findings in six major brain disorders (Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, depression, and autism spectrum disorder). Additionally, we discuss the methodology employed for testing CNS-derived EVs. Among brain disorders, Alzheimer's disease has received the most extensive attention in EV research to date. Most studies focus on specific molecules, candidate proteins, or miRNAs. Notably, the most studied molecules implicated in the pathology of these diseases, such as Aβ, tau, and α-synuclein, exhibit good reproducibility. These findings suggest that CNS-derived EVs can serve as valuable tools for observing brain molecular changes minimally invasively. However, further analysis is necessary to understand the cargo composition of these EVs and improve isolation methods. Therefore, research efforts should prioritize the analysis of CNS-derived EVs' origin and genome-wide biomarker discovery studies.

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References

Ganesh K, Basnet H, Kaygusuz Y, Laughney A, He L, Sharma R . L1CAM defines the regenerative origin of metastasis-initiating cells in colorectal cancer. Nat Cancer. 2020; 1(1):28-45. PMC: 7351134. DOI: 10.1038/s43018-019-0006-x. View

Zou Y, Mu D, Ma X, Wang D, Zhong J, Gao J . Review on the roles of specific cell-derived exosomes in Alzheimer's disease. Front Neurosci. 2022; 16:936760. PMC: 9366882. DOI: 10.3389/fnins.2022.936760. View

Du Y, Tan W, Chen L, Yang Z, Li X, Xue X . Exosome Transplantation From Patients With Schizophrenia Causes Schizophrenia-Relevant Behaviors in Mice: An Integrative Multi-omics Data Analysis. Schizophr Bull. 2021; 47(5):1288-1299. PMC: 8379541. DOI: 10.1093/schbul/sbab039. View

Faure J, Lachenal G, Court M, Hirrlinger J, Chatellard-Causse C, Blot B . Exosomes are released by cultured cortical neurones. Mol Cell Neurosci. 2006; 31(4):642-8. DOI: 10.1016/j.mcn.2005.12.003. View

Dutta S, Hornung S, Kruayatidee A, Maina K, Del Rosario I, Paul K . α-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson's disease from multiple system atrophy. Acta Neuropathol. 2021; 142(3):495-511. PMC: 8357708. DOI: 10.1007/s00401-021-02324-0. View

Hwang S, Lee J . Neuron cell type-specific SNAP-25 expression driven by multiple regulatory elements in the nematode Caenorhabditis elegans. J Mol Biol. 2003; 333(2):237-47. DOI: 10.1016/j.jmb.2003.08.055. View

Jia L, Qiu Q, Zhang H, Chu L, Du Y, Zhang J . Concordance between the assessment of Aβ42, T-tau, and P-T181-tau in peripheral blood neuronal-derived exosomes and cerebrospinal fluid. Alzheimers Dement. 2019; 15(8):1071-1080. DOI: 10.1016/j.jalz.2019.05.002. View

Goetzl E, Abner E, Jicha G, Kapogiannis D, Schwartz J . Declining levels of functionally specialized synaptic proteins in plasma neuronal exosomes with progression of Alzheimer's disease. FASEB J. 2017; 32(2):888-893. PMC: 5888398. DOI: 10.1096/fj.201700731R. View

Kvartsberg H, Duits F, Ingelsson M, Andreasen N, Ohrfelt A, Andersson K . Cerebrospinal fluid levels of the synaptic protein neurogranin correlates with cognitive decline in prodromal Alzheimer's disease. Alzheimers Dement. 2014; 11(10):1180-90. DOI: 10.1016/j.jalz.2014.10.009. View

10.

Shi M, Kovac A, Korff A, Cook T, Ginghina C, Bullock K . CNS tau efflux via exosomes is likely increased in Parkinson's disease but not in Alzheimer's disease. Alzheimers Dement. 2016; 12(11):1125-1131. PMC: 5107127. DOI: 10.1016/j.jalz.2016.04.003. View

11.

Chi H, Yao R, Sun C, Leng B, Shen T, Wang T . Blood Neuroexosomal Mitochondrial Proteins Predict Alzheimer Disease in Diabetes. Diabetes. 2022; 71(6):1313-1323. DOI: 10.2337/db21-0969. View

12.

Dugger B, Dickson D . Pathology of Neurodegenerative Diseases. Cold Spring Harb Perspect Biol. 2017; 9(7). PMC: 5495060. DOI: 10.1101/cshperspect.a028035. View

13.

Jaskiewicz L, Hejne K, Szostak B, Osowiecka K, Skowronski M, Lepiarczyk E . Expression Profiles of AQP3 and AQP4 in Lung Adenocarcinoma Samples Generated via Bronchoscopic Biopsies. J Clin Med. 2022; 11(19). PMC: 9573329. DOI: 10.3390/jcm11195954. View

14.

Jack Jr C, Bennett D, Blennow K, Carrillo M, Dunn B, Budd Haeberlein S . NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018; 14(4):535-562. PMC: 5958625. DOI: 10.1016/j.jalz.2018.02.018. View

15.

Winston C, Goetzl E, Schwartz J, Elahi F, Rissman R . Complement protein levels in plasma astrocyte-derived exosomes are abnormal in conversion from mild cognitive impairment to Alzheimer's disease dementia. Alzheimers Dement (Amst). 2019; 11:61-66. PMC: 6477776. DOI: 10.1016/j.dadm.2018.11.002. View

16.

Sharma K, Schmitt S, Bergner C, Tyanova S, Kannaiyan N, Manrique-Hoyos N . Cell type- and brain region-resolved mouse brain proteome. Nat Neurosci. 2015; 18(12):1819-31. PMC: 7116867. DOI: 10.1038/nn.4160. View

17.

Xie D, Xiong K, Su X, Wang G, Zou Q, Wang L . Glutamate drives 'local Ca release' in cardiac pacemaker cells. Cell Res. 2022; 32(9):843-854. PMC: 9437105. DOI: 10.1038/s41422-022-00693-z. View

18.

Ackermann M, Petrosino J, Manring H, Wright P, Shettigar V, Kilic A . TGF-β1 affects cell-cell adhesion in the heart in an NCAM1-dependent mechanism. J Mol Cell Cardiol. 2017; 112:49-57. PMC: 5647243. DOI: 10.1016/j.yjmcc.2017.08.015. View

19.

Athauda D, Gulyani S, Karnati H, Li Y, Tweedie D, Mustapic M . Utility of Neuronal-Derived Exosomes to Examine Molecular Mechanisms That Affect Motor Function in Patients With Parkinson Disease: A Secondary Analysis of the Exenatide-PD Trial. JAMA Neurol. 2019; 76(4):420-429. PMC: 6459135. DOI: 10.1001/jamaneurol.2018.4304. View

20.

Liberati A, Altman D, Tetzlaff J, Mulrow C, Gotzsche P, Ioannidis J . The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009; 339:b2700. PMC: 2714672. DOI: 10.1136/bmj.b2700. View