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

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 M. J. 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

2 Citations (Scopus)
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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
Article numbere12240
Number of pages12
JournalAlzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Issue number1
Early online date1 Sept 2021
Publication statusPublished - 2021


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


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