
Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals
Author(s) -
Shi Liu,
Buchanan Colin R.,
Cox Simon R.,
Hillary Robert F.,
Marioni Riccardo E.,
Campbell Archie,
Hayward Caroline,
Stolicyn Aleks,
Whalley Heather C.,
Harris Mathew A.,
Waymont Jennifer,
Waiter Gordon,
Backhouse Ellen,
Wardlaw Joanna M.,
Steele Douglas,
Mcintosh Andrew,
Lovestone Simon,
Buckley Noel J.,
NevadoHolgado Alejo J.
Publication year - 2021
Publication title -
alzheimer's and dementia: diagnosis, assessment and disease monitoring
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.497
H-Index - 37
ISSN - 2352-8729
DOI - 10.1002/dad2.12240
Subject(s) - neurodegeneration , hyperintensity , hippocampal formation , disease , pathology , white matter , vascular dementia , neuroscience , psychology , medicine , bioinformatics , biology , magnetic resonance imaging , dementia , radiology
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.