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

Liu Shi; Colin Buchanan; Simon R. Cox; Robert Hillary; Riccardo E Marioni; Archie Campbell; Caroline Hayward; Aleks Stolicyn; Heather Whalley; Mat Harris; Jennifer MJ Waymont; Gordon Waiter; Ellen Backhouse; Joanna M. Wardlaw; Douglas Steele; Andrew M 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, Colin Buchanan, Simon R. Cox, Robert Hillary, Riccardo E Marioni, Archie Campbell, Caroline Hayward, Aleks Stolicyn, Heather Whalley, Mat Harris, Jennifer MJ Waymont, Gordon Waiter, Ellen Backhouse, Joanna M. Wardlaw, Douglas Steele, Andrew M McIntosh, Simon Lovestone, Noel J Buckley, Alejo J Nevado-Holgado

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

Abstract

INTRODUCTION: This study aims to first discover plasma proteomic biomarkers relating to neurodegeneration (N) and vascular (V) damage in cognitively normal individuals and second to discover proteins mediating sex-related difference in N and V pathology.
METHODS: 5032 plasma proteins were measured in 1061 cognitively normal individuals (628 females and 433 males), nearly 90% of whom had magnetic resonance imaging measures of hippocampal volume (as N) and white matter hyperintensities (as V).
RESULTS: Differential protein expression analysis and co-expression network analysis revealed different proteins and modules associated with N and V respectively. Furthermore, causal mediation analysis revealed four proteins mediated sex-related difference in neurodegeneration and one protein mediated such difference in vascular damage.
DISCUSSION: Once validated, the identified proteins could help to select cognitively normal individuals with N and V pathology for Alzheimer’s disease clinical trials and provide targets for further mechanistic studies on brain sex-differences, leading to sex-specific therapeutic strategies.

Original language	English
Journal	Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Early online date	27 Sept 2021
DOIs	https://doi.org/10.1002/dad2.12240
Publication status	Published - 2021

Keywords / Materials (for Non-textual outputs)

plasma proteomics
neurodegeneration
vascular damage
sex-related difference
mediation

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ShiEtalDAADM2021IndentificationOfPlasmaFinal published version, 1.85 MBLicence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

https://doi.org/10.1002/dad2.12240Licence: Creative Commons: Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND)

Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD)
Wardlaw, J. (Principal Investigator)
UK-based charities
1/10/17 → 30/06/19
Project: Research

Cite this

Shi, L., Buchanan, C., Cox, S. R., Hillary, R., Marioni, R. E., Campbell, A., Hayward, C., Stolicyn, A., Whalley, H., Harris, M., Waymont, J. MJ., Waiter, G., Backhouse, E., Wardlaw, J. M., Steele, D., McIntosh, A. M., 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. https://doi.org/10.1002/dad2.12240

@article{07cda7119f524b3ab334fa315608457e,

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 cognitively normal individuals and second to discover proteins mediating sex-related difference in N and V pathology. METHODS: 5032 plasma proteins were measured in 1061 cognitively normal individuals (628 females and 433 males), nearly 90\% of whom had magnetic resonance imaging measures of hippocampal volume (as N) and white matter hyperintensities (as V). RESULTS: Differential protein expression analysis and co-expression network analysis revealed different proteins and modules associated with N and V respectively. Furthermore, causal mediation analysis revealed four proteins mediated sex-related difference in neurodegeneration and one protein mediated such difference in vascular damage. DISCUSSION: Once validated, the identified proteins could help to select cognitively normal individuals with N and V pathology for Alzheimer{\textquoteright}s disease clinical trials and provide targets for further mechanistic studies on brain sex-differences, 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 Robert Hillary and Marioni, \{Riccardo E\} and Archie Campbell and Caroline Hayward and Aleks Stolicyn and Heather Whalley and Mat Harris and Waymont, \{Jennifer MJ\} and Gordon Waiter and Ellen Backhouse and Wardlaw, \{Joanna M.\} and Douglas Steele and McIntosh, \{Andrew M\} and Simon Lovestone and Buckley, \{Noel J\} and Nevado-Holgado, \{Alejo J\}",

year = "2021",

doi = "10.1002/dad2.12240",

language = "English",

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

issn = "2352-8729",

publisher = "Elsevier",

}

Shi, L, Buchanan, C , Cox, SR, Hillary, R, Marioni, RE , Campbell, A , Hayward, C, Stolicyn, A, Whalley, H, Harris, M, Waymont, JMJ, Waiter, G, Backhouse, E, Wardlaw, JM, Steele, D, McIntosh, AM, 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. https://doi.org/10.1002/dad2.12240

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

AU - Marioni, Riccardo E

AU - Campbell, Archie

AU - Hayward, Caroline

AU - Stolicyn, Aleks

AU - Whalley, Heather

AU - Harris, Mat

AU - Waymont, Jennifer MJ

AU - Waiter, Gordon

AU - Backhouse, Ellen

AU - Wardlaw, Joanna M.

AU - Steele, Douglas

AU - McIntosh, Andrew M

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 cognitively normal individuals and second to discover proteins mediating sex-related difference in N and V pathology. METHODS: 5032 plasma proteins were measured in 1061 cognitively normal individuals (628 females and 433 males), nearly 90% of whom had magnetic resonance imaging measures of hippocampal volume (as N) and white matter hyperintensities (as V). RESULTS: Differential protein expression analysis and co-expression network analysis revealed different proteins and modules associated with N and V respectively. Furthermore, causal mediation analysis revealed four proteins mediated sex-related difference in neurodegeneration and one protein mediated such difference in vascular damage. DISCUSSION: Once validated, the identified proteins could help to select cognitively normal individuals with N and V pathology for Alzheimer’s disease clinical trials and provide targets for further mechanistic studies on brain sex-differences, 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 cognitively normal individuals and second to discover proteins mediating sex-related difference in N and V pathology. METHODS: 5032 plasma proteins were measured in 1061 cognitively normal individuals (628 females and 433 males), nearly 90% of whom had magnetic resonance imaging measures of hippocampal volume (as N) and white matter hyperintensities (as V). RESULTS: Differential protein expression analysis and co-expression network analysis revealed different proteins and modules associated with N and V respectively. Furthermore, causal mediation analysis revealed four proteins mediated sex-related difference in neurodegeneration and one protein mediated such difference in vascular damage. DISCUSSION: Once validated, the identified proteins could help to select cognitively normal individuals with N and V pathology for Alzheimer’s disease clinical trials and provide targets for further mechanistic studies on brain sex-differences, 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

SN - 2352-8729

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

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

ER -

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

Abstract

Keywords / Materials (for Non-textual outputs)

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Projects

Rates, Risks and Routes to Reduce Vascular Dementia (R4VaD)

Cite this