Plasma Extracellular Vesicles Enriched for Neuronal Origin: A Potential Window into Brain Pathologic Processes

被引：302
作者：
Mustapic, Maja [1 ]
Eitan, Erez [1 ]
Werner, John K., Jr. [1 ,2 ]
Berkowitz, Sean T. [1 ]
Lazaropoulos, Michael P. [1 ]
Tran, Joyce [1 ]
Goetzl, Edward J. [3 ,4 ]
Kapogiannis, Dimitrios [1 ]
机构：
[1] NIA, Intramural Res Program, Lab Neurosci, NIH, Baltimore, MD 21224 USA
[2] Johns Hopkins Univ, Dept Neurol, Johns Hopkins Sch Med, Baltimore, MD 21218 USA
[3] Univ Calif San Francisco, Dept Med, San Francisco, CA USA
[4] Jewish Home San Francisco, San Francisco, CA USA
来源：
FRONTIERS IN NEUROSCIENCE | 2017年 / 11卷
关键词：
extracellular vesicles (EVs); biological markers; Alzheimer's disease; phosphorylated tau protein; liquid biopsy diagnostics; ALZHEIMERS ASSOCIATION WORKGROUPS; BLOOD EXOSOMES; DIAGNOSTIC GUIDELINES; PATHOGENIC PROTEINS; NATIONAL INSTITUTE; DISEASE; BIOMARKERS; BIODISTRIBUTION; RECOMMENDATIONS; POPULATIONS;
D O I：
10.3389/fnins.2017.00278
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Our team has been a pioneer in harvesting extracellular vesicles (EVs) enriched for neuronal origin from peripheral blood and using them as a biomarker discovery platform for neurological disorders. This methodology has demonstrated excellent diagnostic and predictive performance for Alzheimer's and other neurodegenerative diseases in multiple studies, providing a strong proof of concept for this approach. Here, we describe our methodology in detail and offer further evidence that isolated EVs are enriched for neuronal origin. In addition, we present evidence that EVs enriched for neuronal origin represent a more sensitive and accurate base for biomarkers than plasma, serum, or non-enriched total plasma EVs. Finally, we proceed to investigate the protein content of EVs enriched for neuronal origin and compare it with other relevant enriched and non-enriched populations of plasma EVs. Neuronal-origin enriched plasma EVs contain higher levels of signaling molecules of great interest for cellular metabolism, survival, and repair, which may be useful as biomarkers and to follow response to therapeutic interventions in a mechanism-specific manner.
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页数：12
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共 43 条
  • [1] Plasma neuronal exosomal levels of Alzheimer's disease biomarkers in normal aging
    Abner, Erin L.
    Jicha, Gregory A.
    Shaw, Leslie M.
    Trojanowski, John Q.
    Goetzl, Edward J.
    [J]. ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY, 2016, 3 (05): : 399 - 403
  • [2] Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes
    Alvarez-Erviti, Lydia
    Seow, Yiqi
    Yin, HaiFang
    Betts, Corinne
    Lakhal, Samira
    Wood, Matthew J. A.
    [J]. NATURE BIOTECHNOLOGY, 2011, 29 (04) : 341 - U179
  • [3] The Topographical and Neuroanatomical Distribution of Neurofibrillary Tangles and Neuritic Plaques in the Cerebral Cortex of Patients with Alzheimer's Disease
    Arnold, Steven E.
    Hyman, Bradley T.
    Flory, Jill
    Damasio, Antonio R.
    Van Hoesen, Gary W.
    [J]. CEREBRAL CORTEX, 1991, 1 (01) : 103 - 116
  • [4] Biodistribution and function of extracellular miRNA-155 in mice
    Bala, Shashi
    Csak, Timea
    Momen-Heravi, Fatemeh
    Lippai, Dora
    Kodys, Karen
    Catalano, Donna
    Satishchandran, Abhishek
    Ambros, Victor
    Szabo, Gyongyi
    [J]. SCIENTIFIC REPORTS, 2015, 5
  • [5] BDNF is essential to promote persistence of long-term memory storage
    Bekinschtein, Pedro
    Cammarota, Martin
    Katche, Cynthia
    Slipczuk, Leandro
    Rossato, Janine I.
    Goldin, Andrea
    Lzquierdo, Ivan
    Medina, Jorge H.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2008, 105 (07) : 2711 - 2716
  • [6] Exosomes: vehicles for the transfer of toxic proteins associated with neurodegenerative diseases?
    Bellingham, Shayne A.
    Guo, Belinda B.
    Coleman, Bradley M.
    Hill, Andrew F.
    [J]. FRONTIERS IN PHYSIOLOGY, 2012, 3
  • [7] NEUROPATHOLOGICAL STAGING OF ALZHEIMER-RELATED CHANGES
    BRAAK, H
    BRAAK, E
    [J]. ACTA NEUROPATHOLOGICA, 1991, 82 (04) : 239 - 259
  • [8] Where, when, and in what form does sporadic Alzheimer's disease begin?
    Braak, Heiko
    Del Tredici, Kelly
    [J]. CURRENT OPINION IN NEUROLOGY, 2012, 25 (06) : 708 - 714
  • [9] Elucidation of Exosome Migration Across the Blood-Brain Barrier Model In Vitro
    Chen, Claire C.
    Liu, Linan
    Ma, Fengxia
    Wong, Chi W.
    Guo, Xuning E.
    Chacko, Jenu V.
    Farhoodi, Henry P.
    Zhang, Shirley X.
    Zimak, Jan
    Segaliny, Aude
    Riazifar, Milad
    Pham, Victor
    Digman, Michelle A.
    Pone, Egest J.
    Zhao, Weian
    [J]. CELLULAR AND MOLECULAR BIOENGINEERING, 2016, 9 (04) : 509 - 529
  • [10] BEAMing and Droplet Digital PCR Analysis of Mutant IDH1 mRNA in Glioma Patient Serum and Cerebrospinal Fluid Extracellular Vesicles
    Chen, Walter W.
    Balaj, Leonora
    Liau, Linda M.
    Samuels, Michael L.
    Kotsopoulos, Steve K.
    Maguire, Casey A.
    LoGuidice, Lori
    Soto, Horacio
    Garrett, Matthew
    Zhu, Lin Dan
    Sivaraman, Sarada
    Chen, Clark
    Wong, Eric T.
    Carter, Bob S.
    Hochberg, Fred H.
    Breakefield, Xandra O.
    Skog, Johan
    [J]. MOLECULAR THERAPY-NUCLEIC ACIDS, 2013, 2 : e109
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