Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues

Satoshi Muraoka; Annina M. DeLeo; Manveen K. Sethi; Kayo Yukawa-Takamatsu; Zijian Yang; Jina Ko; John D. Hogan; Zhi Ruan; Yang You; Yuzhi Wang; Maria Medalla; Seiko Ikezu; Mei Chen; Weiming Xia; Santhi Gorantla; Howard E. Gendelman; David Issadore; Joseph Zaia; Tsuneya Ikezu

doi:10.1002/alz.12089

Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues

Satoshi Muraoka, Annina M. DeLeo, Manveen K. Sethi, Kayo Yukawa-Takamatsu, Zijian Yang, Jina Ko, John D. Hogan, Zhi Ruan, Yang You, Yuzhi Wang, Maria Medalla, Seiko Ikezu, Mei Chen, Weiming Xia, Santhi Gorantla, Howard E. Gendelman, David Issadore, Joseph Zaia, Tsuneya Ikezu

Neuroscience

Research output: Contribution to journal › Article › peer-review

Abstract

Introduction: Extracellular vesicles (EVs) from human Alzheimer's disease (AD) biospecimens contain amyloid beta (Aβ) peptide and tau. While AD EVs are known to affect brain disease pathobiology, their biochemical and molecular characterizations remain ill defined. Methods: EVs were isolated from the cortical gray matter of 20 AD and 18 control brains. Tau and Aβ levels were measured by immunoassay. Differentially expressed EV proteins were assessed by quantitative proteomics and machine learning. Results: Levels of pS396 tau and Aβ1–42 were significantly elevated in AD EVs. High levels of neuron- and glia-specific factors are detected in control and AD EVs, respectively. Machine learning identified ANXA5, VGF, GPM6A, and ACTZ in AD EV compared to controls. They distinguished AD EVs from controls in the test sets with 88% accuracy. Discussion: In addition to Aβ and tau, ANXA5, VGF, GPM6A, and ACTZ are new signature proteins in AD EVs.

Original language	English (US)
Pages (from-to)	896-907
Number of pages	12
Journal	Alzheimer's and Dementia
Volume	16
Issue number	6
DOIs	https://doi.org/10.1002/alz.12089
State	Published - Jun 1 2020

Keywords

Alzheimer's disease
amyloid beta peptide
cortical gray matter
extracellular vesicles
machine learning
microtubule-associated protein tau
proteome

ASJC Scopus subject areas

Epidemiology
Health Policy
Developmental Neuroscience
Clinical Neurology
Geriatrics and Gerontology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1002/alz.12089

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Muraoka, S., DeLeo, A. M., Sethi, M. K., Yukawa-Takamatsu, K., Yang, Z., Ko, J., Hogan, J. D., Ruan, Z., You, Y., Wang, Y., Medalla, M., Ikezu, S., Chen, M., Xia, W., Gorantla, S., Gendelman, H. E., Issadore, D., Zaia, J., & Ikezu, T. (2020). Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues. Alzheimer's and Dementia, 16(6), 896-907. https://doi.org/10.1002/alz.12089

Muraoka, S, DeLeo, AM, Sethi, MK, Yukawa-Takamatsu, K, Yang, Z, Ko, J, Hogan, JD, Ruan, Z, You, Y, Wang, Y, Medalla, M, Ikezu, S, Chen, M, Xia, W, Gorantla, S, Gendelman, HE, Issadore, D, Zaia, J & Ikezu, T 2020, 'Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues', Alzheimer's and Dementia, vol. 16, no. 6, pp. 896-907. https://doi.org/10.1002/alz.12089

@article{281d09119fe744f093b938cbcb87594d,

title = "Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues",

abstract = "Introduction: Extracellular vesicles (EVs) from human Alzheimer's disease (AD) biospecimens contain amyloid beta (Aβ) peptide and tau. While AD EVs are known to affect brain disease pathobiology, their biochemical and molecular characterizations remain ill defined. Methods: EVs were isolated from the cortical gray matter of 20 AD and 18 control brains. Tau and Aβ levels were measured by immunoassay. Differentially expressed EV proteins were assessed by quantitative proteomics and machine learning. Results: Levels of pS396 tau and Aβ1–42 were significantly elevated in AD EVs. High levels of neuron- and glia-specific factors are detected in control and AD EVs, respectively. Machine learning identified ANXA5, VGF, GPM6A, and ACTZ in AD EV compared to controls. They distinguished AD EVs from controls in the test sets with 88% accuracy. Discussion: In addition to Aβ and tau, ANXA5, VGF, GPM6A, and ACTZ are new signature proteins in AD EVs.",

keywords = "Alzheimer's disease, amyloid beta peptide, cortical gray matter, extracellular vesicles, machine learning, microtubule-associated protein tau, proteome",

author = "Satoshi Muraoka and DeLeo, {Annina M.} and Sethi, {Manveen K.} and Kayo Yukawa-Takamatsu and Zijian Yang and Jina Ko and Hogan, {John D.} and Zhi Ruan and Yang You and Yuzhi Wang and Maria Medalla and Seiko Ikezu and Mei Chen and Weiming Xia and Santhi Gorantla and Gendelman, {Howard E.} and David Issadore and Joseph Zaia and Tsuneya Ikezu",

note = "Funding Information: This work is in part funded by Alzheimer's Association AARF‐9550302678 (AMD & SM), DVT‐14‐320835 (TI), BrightFocus Foundation (A2016551S), Cure Alzheimer's Fund (TI), National Institute of Health (NIH), National Institute in Aging (NIA) and National Institute of Neurological Disorders and Stroke (NINDS) RF1AG054199 (TI), NIH R56AG057469 (TI), NIH R01AG054672 (TI), NIH R21NS104609 (TI). Funding Information: The author thanks Maria Ericsson (Electron Microscopy Facility, Harvard Medical School) for electron microscopic imaging services, participating laboratories of NIH NeuroBioBank for providing frozen human brain tissue specimens, and Li Wu (University of Nebraska Medical Center) for providing human brain tissue specimens. This work is in part funded by Alzheimer's Association AARF-9550302678 (AMD & SM), DVT-14-320835 (TI), BrightFocus Foundation (A2016551S), Cure Alzheimer's Fund (TI), National Institute of Health (NIH), National Institute in Aging (NIA) and National Institute of Neurological Disorders and Stroke (NINDS) RF1AG054199 (TI), NIH R56AG057469 (TI), NIH R01AG054672 (TI), NIH R21NS104609 (TI). Tsuneya Ikezu collaborates with Abbvie Inc. (USA), Aethlone Medical, Inc. (USA), Eisai (Japan/USA) and Ono Pharmaceutical (Japan), and consults Takeda (Japan/USA). Publisher Copyright: {\textcopyright} 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.",

year = "2020",

month = jun,

day = "1",

doi = "10.1002/alz.12089",

language = "English (US)",

volume = "16",

pages = "896--907",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

publisher = "Elsevier Inc.",

number = "6",

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TY - JOUR

T1 - Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues

AU - Muraoka, Satoshi

AU - DeLeo, Annina M.

AU - Sethi, Manveen K.

AU - Yukawa-Takamatsu, Kayo

AU - Yang, Zijian

AU - Ko, Jina

AU - Hogan, John D.

AU - Ruan, Zhi

AU - You, Yang

AU - Wang, Yuzhi

AU - Medalla, Maria

AU - Ikezu, Seiko

AU - Chen, Mei

AU - Xia, Weiming

AU - Gorantla, Santhi

AU - Gendelman, Howard E.

AU - Issadore, David

AU - Zaia, Joseph

AU - Ikezu, Tsuneya

N1 - Funding Information: This work is in part funded by Alzheimer's Association AARF‐9550302678 (AMD & SM), DVT‐14‐320835 (TI), BrightFocus Foundation (A2016551S), Cure Alzheimer's Fund (TI), National Institute of Health (NIH), National Institute in Aging (NIA) and National Institute of Neurological Disorders and Stroke (NINDS) RF1AG054199 (TI), NIH R56AG057469 (TI), NIH R01AG054672 (TI), NIH R21NS104609 (TI). Funding Information: The author thanks Maria Ericsson (Electron Microscopy Facility, Harvard Medical School) for electron microscopic imaging services, participating laboratories of NIH NeuroBioBank for providing frozen human brain tissue specimens, and Li Wu (University of Nebraska Medical Center) for providing human brain tissue specimens. This work is in part funded by Alzheimer's Association AARF-9550302678 (AMD & SM), DVT-14-320835 (TI), BrightFocus Foundation (A2016551S), Cure Alzheimer's Fund (TI), National Institute of Health (NIH), National Institute in Aging (NIA) and National Institute of Neurological Disorders and Stroke (NINDS) RF1AG054199 (TI), NIH R56AG057469 (TI), NIH R01AG054672 (TI), NIH R21NS104609 (TI). Tsuneya Ikezu collaborates with Abbvie Inc. (USA), Aethlone Medical, Inc. (USA), Eisai (Japan/USA) and Ono Pharmaceutical (Japan), and consults Takeda (Japan/USA). Publisher Copyright: © 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.

PY - 2020/6/1

Y1 - 2020/6/1

N2 - Introduction: Extracellular vesicles (EVs) from human Alzheimer's disease (AD) biospecimens contain amyloid beta (Aβ) peptide and tau. While AD EVs are known to affect brain disease pathobiology, their biochemical and molecular characterizations remain ill defined. Methods: EVs were isolated from the cortical gray matter of 20 AD and 18 control brains. Tau and Aβ levels were measured by immunoassay. Differentially expressed EV proteins were assessed by quantitative proteomics and machine learning. Results: Levels of pS396 tau and Aβ1–42 were significantly elevated in AD EVs. High levels of neuron- and glia-specific factors are detected in control and AD EVs, respectively. Machine learning identified ANXA5, VGF, GPM6A, and ACTZ in AD EV compared to controls. They distinguished AD EVs from controls in the test sets with 88% accuracy. Discussion: In addition to Aβ and tau, ANXA5, VGF, GPM6A, and ACTZ are new signature proteins in AD EVs.

AB - Introduction: Extracellular vesicles (EVs) from human Alzheimer's disease (AD) biospecimens contain amyloid beta (Aβ) peptide and tau. While AD EVs are known to affect brain disease pathobiology, their biochemical and molecular characterizations remain ill defined. Methods: EVs were isolated from the cortical gray matter of 20 AD and 18 control brains. Tau and Aβ levels were measured by immunoassay. Differentially expressed EV proteins were assessed by quantitative proteomics and machine learning. Results: Levels of pS396 tau and Aβ1–42 were significantly elevated in AD EVs. High levels of neuron- and glia-specific factors are detected in control and AD EVs, respectively. Machine learning identified ANXA5, VGF, GPM6A, and ACTZ in AD EV compared to controls. They distinguished AD EVs from controls in the test sets with 88% accuracy. Discussion: In addition to Aβ and tau, ANXA5, VGF, GPM6A, and ACTZ are new signature proteins in AD EVs.

KW - Alzheimer's disease

KW - amyloid beta peptide

KW - cortical gray matter

KW - extracellular vesicles

KW - machine learning

KW - microtubule-associated protein tau

KW - proteome

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U2 - 10.1002/alz.12089

DO - 10.1002/alz.12089

M3 - Article

C2 - 32301581

AN - SCOPUS:85083517781

SN - 1552-5260

VL - 16

SP - 896

EP - 907

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 6

ER -

Proteomic and biological profiling of extracellular vesicles from Alzheimer's disease human brain tissues

Abstract

Keywords

ASJC Scopus subject areas

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