Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals

Liu Shi; Colin Buchanan; Simon R. Cox; Robert F. Hillary; Riccardo E.  Marioni; Archie Campbell; Caroline Hayward; Aleks Stolicyn; Heather C. Whalley; Jennifer M. J. Waymont; Gordon D. Waiter; Ellen V . Backhouse; Douglas Steele; Andrew Mcintosh; Simon  Lovestone; Noel J. Buckley; Alejo J. Nevado-Holgado

doi:10.1002/dad2.12240

Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals

Liu Shi (Lead / Corresponding author), Colin Buchanan, Simon R. Cox, Robert F. Hillary, Riccardo E. Marioni, Archie Campbell, Caroline Hayward, Aleks Stolicyn, Heather C. Whalley, Jennifer M. J. Waymont, Gordon D. Waiter, Ellen V . Backhouse, Douglas Steele, Andrew Mcintosh, Simon Lovestone, Noel J. Buckley, Alejo J. Nevado-Holgado

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Abstract

Introduction: This study aims to first discover plasma proteomic biomarkers relating to neurodegeneration (N) and vascular (V) damage in pre-clinical Alzheimer’s disease (AD) and second to discover proteins mediating sex related difference in N and V pathology.

Methods: 5033 plasma proteins were measured in 1061 cognitively normal individuals (628 female and 433 male), nearly 90% of whom had magnetic resonance imaging (MRI) measures of hippocampus volume (as N) and white matter hyperintensities (as V).

Results: Protein differential analysis and co-expression network analysis revealed several proteins and modules associated with N and V respectively and such associations were affected by sex. Furthermore, four proteins mediated sex-related difference in neurodegeneration and one protein mediated such difference in vascular damage.

Discussion: The identified proteins could help to select cognitively normal individuals with N and V pathology for AD clinical trials and provide tractable targets for further mechanistic studies, leading to sex-specific therapeutic strategies

Original language	English
Article number	e12240
Number of pages	12
Journal	Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Volume	13
Issue number	1
Early online date	1 Sept 2021
DOIs	https://doi.org/10.1002/dad2.12240
Publication status	Published - 2021

Keywords

plasma proteomics
neurodegeneration
vascular damage
sex-related difference
mediation

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10.1002/dad2.12240Licence: CC BY-NC-ND

Final Published VersionFinal published version, 1.85 MBLicence: CC BY-NC-ND

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MICA: InterdisciPlInary Collaboration for EfficienT and Effective Use of Clinical Images in Big Data Health Care RESearch: PICTURES (Programme Grant) (Joint with Universities of Edinburgh and Abertay)
Doney, A. (Investigator), Jefferson, E. (Investigator), Palmer, C. (Investigator), Steele, D. (Investigator), Trucco, M. (Investigator) & Wang, H. (Investigator)
Medical Research Council
1/08/19 → 28/02/25
Project: Research
STRADL - Provision of MRI Scans
Steele, D. (Investigator)
23/06/16 → 23/07/19
Project: Research

Cite this

Shi, L., Buchanan, C., Cox, S. R., Hillary, R. F., Marioni, R. E., Campbell, A., Hayward, C., Stolicyn, A., Whalley, H. C., Waymont, J. M. J., Waiter, G. D., Backhouse, E. V. ., Steele, D., Mcintosh, A., Lovestone, S., Buckley, N. J., & Nevado-Holgado, A. J. (2021). Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, 13(1), Article e12240. https://doi.org/10.1002/dad2.12240

@article{202aa061bbbe4f50bb456b2327a1d944,

title = "Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals",

abstract = "Introduction: This study aims to first discover plasma proteomic biomarkers relating to neurodegeneration (N) and vascular (V) damage in pre-clinical Alzheimer{\textquoteright}s disease (AD) and second to discover proteins mediating sex related difference in N and V pathology.Methods: 5033 plasma proteins were measured in 1061 cognitively normal individuals (628 female and 433 male), nearly 90% of whom had magnetic resonance imaging (MRI) measures of hippocampus volume (as N) and white matter hyperintensities (as V).Results: Protein differential analysis and co-expression network analysis revealed several proteins and modules associated with N and V respectively and such associations were affected by sex. Furthermore, four proteins mediated sex-related difference in neurodegeneration and one protein mediated such difference in vascular damage.Discussion: The identified proteins could help to select cognitively normal individuals with N and V pathology for AD clinical trials and provide tractable targets for further mechanistic studies, leading to sex-specific therapeutic strategies",

keywords = "plasma proteomics, neurodegeneration, vascular damage, sex-related difference, mediation",

author = "Liu Shi and Colin Buchanan and Cox, {Simon R.} and Hillary, {Robert F.} and Marioni, {Riccardo E.} and Archie Campbell and Caroline Hayward and Aleks Stolicyn and Whalley, {Heather C.} and Waymont, {Jennifer M. J.} and Waiter, {Gordon D.} and Backhouse, {Ellen V .} and Douglas Steele and Andrew Mcintosh and Simon Lovestone and Buckley, {Noel J.} and Nevado-Holgado, {Alejo J.}",

year = "2021",

doi = "10.1002/dad2.12240",

language = "English",

volume = "13",

journal = "Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring",

issn = "2352-8729",

publisher = "Wiley",

number = "1",

}

Shi, L, Buchanan, C, Cox, SR, Hillary, RF, Marioni, RE, Campbell, A, Hayward, C, Stolicyn, A, Whalley, HC, Waymont, JMJ, Waiter, GD, Backhouse, EV, Steele, D, Mcintosh, A, Lovestone, S, Buckley, NJ & Nevado-Holgado, AJ 2021, 'Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals', Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, vol. 13, no. 1, e12240. https://doi.org/10.1002/dad2.12240

Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals. / Shi, Liu (Lead / Corresponding author); Buchanan, Colin; Cox, Simon R. et al.
In: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Vol. 13, No. 1, e12240, 2021.

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

TY - JOUR

T1 - Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals

AU - Shi, Liu

AU - Buchanan, Colin

AU - Cox, Simon R.

AU - Hillary, Robert F.

AU - Marioni, Riccardo E.

AU - Campbell, Archie

AU - Hayward, Caroline

AU - Stolicyn, Aleks

AU - Whalley, Heather C.

AU - Waymont, Jennifer M. J.

AU - Waiter, Gordon D.

AU - Backhouse, Ellen V .

AU - Steele, Douglas

AU - Mcintosh, Andrew

AU - Lovestone, Simon

AU - Buckley, Noel J.

AU - Nevado-Holgado, Alejo J.

PY - 2021

Y1 - 2021

N2 - Introduction: This study aims to first discover plasma proteomic biomarkers relating to neurodegeneration (N) and vascular (V) damage in pre-clinical Alzheimer’s disease (AD) and second to discover proteins mediating sex related difference in N and V pathology.Methods: 5033 plasma proteins were measured in 1061 cognitively normal individuals (628 female and 433 male), nearly 90% of whom had magnetic resonance imaging (MRI) measures of hippocampus volume (as N) and white matter hyperintensities (as V).Results: Protein differential analysis and co-expression network analysis revealed several proteins and modules associated with N and V respectively and such associations were affected by sex. Furthermore, four proteins mediated sex-related difference in neurodegeneration and one protein mediated such difference in vascular damage.Discussion: The identified proteins could help to select cognitively normal individuals with N and V pathology for AD clinical trials and provide tractable targets for further mechanistic studies, leading to sex-specific therapeutic strategies

AB - Introduction: This study aims to first discover plasma proteomic biomarkers relating to neurodegeneration (N) and vascular (V) damage in pre-clinical Alzheimer’s disease (AD) and second to discover proteins mediating sex related difference in N and V pathology.Methods: 5033 plasma proteins were measured in 1061 cognitively normal individuals (628 female and 433 male), nearly 90% of whom had magnetic resonance imaging (MRI) measures of hippocampus volume (as N) and white matter hyperintensities (as V).Results: Protein differential analysis and co-expression network analysis revealed several proteins and modules associated with N and V respectively and such associations were affected by sex. Furthermore, four proteins mediated sex-related difference in neurodegeneration and one protein mediated such difference in vascular damage.Discussion: The identified proteins could help to select cognitively normal individuals with N and V pathology for AD clinical trials and provide tractable targets for further mechanistic studies, leading to sex-specific therapeutic strategies

KW - plasma proteomics

KW - neurodegeneration

KW - vascular damage

KW - sex-related difference

KW - mediation

U2 - 10.1002/dad2.12240

DO - 10.1002/dad2.12240

M3 - Article

C2 - 34604499

SN - 2352-8729

VL - 13

JO - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

JF - Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

IS - 1

M1 - e12240

ER -

Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals

Abstract

Keywords

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Projects

MICA: InterdisciPlInary Collaboration for EfficienT and Effective Use of Clinical Images in Big Data Health Care RESearch: PICTURES (Programme Grant) (Joint with Universities of Edinburgh and Abertay)

STRADL - Provision of MRI Scans

Cite this