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

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

123 Scopus citations

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

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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",

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year = "2020",

month = jun,

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doi = "10.1002/alz.12089",

language = "English (US)",

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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

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

Abstract

Keywords

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