Identification of plasma proteins mediating sex-related differences in human brain neurodegeneration (N) and vascular (V) pathology

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

Research output: Contribution to journalArticlepeer-review


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 languageEnglish
JournalAlzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Publication statusAccepted/In press - 18 Aug 2021


  • plasma proteomics
  • neurodegeneration
  • vascular damage
  • sex-related difference
  • mediation


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