Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer's Disease Pathology in Older Adults

Loïc Dayon, Jérôme Wojcik, Antonio Núñez Galindo, John Corthésy, Ornella Cominetti, Aikaterini Oikonomidi, Hugues Henry, Eugenia Migliavacca, Gene Bowman, Julius Popp

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background: Cerebrospinal fluid (CSF) biomarkers of the beta-amyloid and microtubule associated protein tau metabolism have proven the capacity to improve classification of subjects developing Alzheimer's disease (AD). The blood plasma proteome was characterized to further elaborate upon the mechanisms involved and identify proteins that may improve classification of older adults developing an AD dementia. Objective: Identify and describe plasma protein expressions that best classify subjects with CSF-defined presence of AD pathology and cerebral amyloidosis. Methods: We performed a cross-sectional analysis of samples collected from community-dwelling elderly with (n = 72) or without (n = 48) cognitive impairment. CSF Aβ 1-42, tau, and phosphorylated tau (P-tau181) were measured using ELISA, and mass spectrometry quantified the plasma proteomes. Presence of AD pathology was defined as CSF P-tau181/Aβ 1-42 > 0.0779, and presence of amyloidosis was defined as CSF Aβ 1-42 < 724 pg/mL. Results: Two hundred and forty-eight plasma proteins were quantified. Plasma proteins did not improve classification of the AD CSF biomarker profile in the whole sample. When the analysis was separately performed in the cognitively impaired individuals, the diagnosis accuracy of AD CSF profile was 88.9% with 19 plasma proteins included. Within the full cohort, there were 16 plasma proteins that improved diagnostic accuracy of cerebral amyloidosis to 92.4%. Conclusion: Plasma proteins improved classification accuracy of AD pathology in cognitively-impaired older adults and appeared representative of amyloid pathology. If confirmed, those candidates could serve as valuable blood biomarkers of the preclinical stages of AD or risk of developing AD.

Original languageEnglish (US)
Pages (from-to)1641-1652
Number of pages12
JournalJournal of Alzheimer's Disease
Volume60
Issue number4
DOIs
StatePublished - 2017
Externally publishedYes

Fingerprint

Proteomics
Cerebrospinal Fluid
Alzheimer Disease
Pathology
Blood Proteins
Biomarkers
Proteome
Amyloid
Independent Living
Microtubule-Associated Proteins
Amyloidosis
Mass Spectrometry
Cross-Sectional Studies
Enzyme-Linked Immunosorbent Assay

Keywords

  • Alzheimer's disease
  • amyloid-β
  • amyloidosis
  • biomarker
  • dementia
  • protein
  • tau

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

Dayon, L., Wojcik, J., Núñez Galindo, A., Corthésy, J., Cominetti, O., Oikonomidi, A., ... Popp, J. (2017). Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer's Disease Pathology in Older Adults. Journal of Alzheimer's Disease, 60(4), 1641-1652. https://doi.org/10.3233/JAD-170426

Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer's Disease Pathology in Older Adults. / Dayon, Loïc; Wojcik, Jérôme; Núñez Galindo, Antonio; Corthésy, John; Cominetti, Ornella; Oikonomidi, Aikaterini; Henry, Hugues; Migliavacca, Eugenia; Bowman, Gene; Popp, Julius.

In: Journal of Alzheimer's Disease, Vol. 60, No. 4, 2017, p. 1641-1652.

Research output: Contribution to journalArticle

Dayon, L, Wojcik, J, Núñez Galindo, A, Corthésy, J, Cominetti, O, Oikonomidi, A, Henry, H, Migliavacca, E, Bowman, G & Popp, J 2017, 'Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer's Disease Pathology in Older Adults', Journal of Alzheimer's Disease, vol. 60, no. 4, pp. 1641-1652. https://doi.org/10.3233/JAD-170426
Dayon, Loïc ; Wojcik, Jérôme ; Núñez Galindo, Antonio ; Corthésy, John ; Cominetti, Ornella ; Oikonomidi, Aikaterini ; Henry, Hugues ; Migliavacca, Eugenia ; Bowman, Gene ; Popp, Julius. / Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer's Disease Pathology in Older Adults. In: Journal of Alzheimer's Disease. 2017 ; Vol. 60, No. 4. pp. 1641-1652.
@article{e3e16cdf4bf1454fbe178dee9ff43846,
title = "Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer's Disease Pathology in Older Adults",
abstract = "Background: Cerebrospinal fluid (CSF) biomarkers of the beta-amyloid and microtubule associated protein tau metabolism have proven the capacity to improve classification of subjects developing Alzheimer's disease (AD). The blood plasma proteome was characterized to further elaborate upon the mechanisms involved and identify proteins that may improve classification of older adults developing an AD dementia. Objective: Identify and describe plasma protein expressions that best classify subjects with CSF-defined presence of AD pathology and cerebral amyloidosis. Methods: We performed a cross-sectional analysis of samples collected from community-dwelling elderly with (n = 72) or without (n = 48) cognitive impairment. CSF Aβ 1-42, tau, and phosphorylated tau (P-tau181) were measured using ELISA, and mass spectrometry quantified the plasma proteomes. Presence of AD pathology was defined as CSF P-tau181/Aβ 1-42 > 0.0779, and presence of amyloidosis was defined as CSF Aβ 1-42 < 724 pg/mL. Results: Two hundred and forty-eight plasma proteins were quantified. Plasma proteins did not improve classification of the AD CSF biomarker profile in the whole sample. When the analysis was separately performed in the cognitively impaired individuals, the diagnosis accuracy of AD CSF profile was 88.9{\%} with 19 plasma proteins included. Within the full cohort, there were 16 plasma proteins that improved diagnostic accuracy of cerebral amyloidosis to 92.4{\%}. Conclusion: Plasma proteins improved classification accuracy of AD pathology in cognitively-impaired older adults and appeared representative of amyloid pathology. If confirmed, those candidates could serve as valuable blood biomarkers of the preclinical stages of AD or risk of developing AD.",
keywords = "Alzheimer's disease, amyloid-β, amyloidosis, biomarker, dementia, protein, tau",
author = "Lo{\"i}c Dayon and J{\'e}r{\^o}me Wojcik and {N{\'u}{\~n}ez Galindo}, Antonio and John Corth{\'e}sy and Ornella Cominetti and Aikaterini Oikonomidi and Hugues Henry and Eugenia Migliavacca and Gene Bowman and Julius Popp",
year = "2017",
doi = "10.3233/JAD-170426",
language = "English (US)",
volume = "60",
pages = "1641--1652",
journal = "Journal of Alzheimer's Disease",
issn = "1387-2877",
publisher = "IOS Press",
number = "4",

}

TY - JOUR

T1 - Plasma Proteomic Profiles of Cerebrospinal Fluid-Defined Alzheimer's Disease Pathology in Older Adults

AU - Dayon, Loïc

AU - Wojcik, Jérôme

AU - Núñez Galindo, Antonio

AU - Corthésy, John

AU - Cominetti, Ornella

AU - Oikonomidi, Aikaterini

AU - Henry, Hugues

AU - Migliavacca, Eugenia

AU - Bowman, Gene

AU - Popp, Julius

PY - 2017

Y1 - 2017

N2 - Background: Cerebrospinal fluid (CSF) biomarkers of the beta-amyloid and microtubule associated protein tau metabolism have proven the capacity to improve classification of subjects developing Alzheimer's disease (AD). The blood plasma proteome was characterized to further elaborate upon the mechanisms involved and identify proteins that may improve classification of older adults developing an AD dementia. Objective: Identify and describe plasma protein expressions that best classify subjects with CSF-defined presence of AD pathology and cerebral amyloidosis. Methods: We performed a cross-sectional analysis of samples collected from community-dwelling elderly with (n = 72) or without (n = 48) cognitive impairment. CSF Aβ 1-42, tau, and phosphorylated tau (P-tau181) were measured using ELISA, and mass spectrometry quantified the plasma proteomes. Presence of AD pathology was defined as CSF P-tau181/Aβ 1-42 > 0.0779, and presence of amyloidosis was defined as CSF Aβ 1-42 < 724 pg/mL. Results: Two hundred and forty-eight plasma proteins were quantified. Plasma proteins did not improve classification of the AD CSF biomarker profile in the whole sample. When the analysis was separately performed in the cognitively impaired individuals, the diagnosis accuracy of AD CSF profile was 88.9% with 19 plasma proteins included. Within the full cohort, there were 16 plasma proteins that improved diagnostic accuracy of cerebral amyloidosis to 92.4%. Conclusion: Plasma proteins improved classification accuracy of AD pathology in cognitively-impaired older adults and appeared representative of amyloid pathology. If confirmed, those candidates could serve as valuable blood biomarkers of the preclinical stages of AD or risk of developing AD.

AB - Background: Cerebrospinal fluid (CSF) biomarkers of the beta-amyloid and microtubule associated protein tau metabolism have proven the capacity to improve classification of subjects developing Alzheimer's disease (AD). The blood plasma proteome was characterized to further elaborate upon the mechanisms involved and identify proteins that may improve classification of older adults developing an AD dementia. Objective: Identify and describe plasma protein expressions that best classify subjects with CSF-defined presence of AD pathology and cerebral amyloidosis. Methods: We performed a cross-sectional analysis of samples collected from community-dwelling elderly with (n = 72) or without (n = 48) cognitive impairment. CSF Aβ 1-42, tau, and phosphorylated tau (P-tau181) were measured using ELISA, and mass spectrometry quantified the plasma proteomes. Presence of AD pathology was defined as CSF P-tau181/Aβ 1-42 > 0.0779, and presence of amyloidosis was defined as CSF Aβ 1-42 < 724 pg/mL. Results: Two hundred and forty-eight plasma proteins were quantified. Plasma proteins did not improve classification of the AD CSF biomarker profile in the whole sample. When the analysis was separately performed in the cognitively impaired individuals, the diagnosis accuracy of AD CSF profile was 88.9% with 19 plasma proteins included. Within the full cohort, there were 16 plasma proteins that improved diagnostic accuracy of cerebral amyloidosis to 92.4%. Conclusion: Plasma proteins improved classification accuracy of AD pathology in cognitively-impaired older adults and appeared representative of amyloid pathology. If confirmed, those candidates could serve as valuable blood biomarkers of the preclinical stages of AD or risk of developing AD.

KW - Alzheimer's disease

KW - amyloid-β

KW - amyloidosis

KW - biomarker

KW - dementia

KW - protein

KW - tau

UR - http://www.scopus.com/inward/record.url?scp=85033600001&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85033600001&partnerID=8YFLogxK

U2 - 10.3233/JAD-170426

DO - 10.3233/JAD-170426

M3 - Article

C2 - 29125490

AN - SCOPUS:85033600001

VL - 60

SP - 1641

EP - 1652

JO - Journal of Alzheimer's Disease

JF - Journal of Alzheimer's Disease

SN - 1387-2877

IS - 4

ER -