Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals.
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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
Five thousand and thirty-two 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 N and one protein mediated such difference in V 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.
SUBMITTER: Shi L
PROVIDER: S-EPMC8474123 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals.
Shi Liu L Buchanan Colin R CR Cox Simon R SR Hillary Robert F RF Marioni Riccardo E RE Campbell Archie A Hayward Caroline C Stolicyn Aleks A Whalley Heather C HC Harris Mathew A MA Waymont Jennifer J Waiter Gordon G Backhouse Ellen E Wardlaw Joanna M JM Steele Douglas D Mcintosh Andrew A Lovestone Simon S Buckley Noel J NJ Nevado-Holgado Alejo J AJ
Alzheimer's & dementia (Amsterdam, Netherlands) 20210927 1
<h4>Introduction</h4>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.<h4>Methods</h4>Five thousand and thirty-two 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 whit ...[more]
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