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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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.

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).

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.

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 languageEnglish
Article numbere12240
Number of pages12
JournalAlzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Issue number1
Publication statusPublished - 27 Sep 2021


  • meditation
  • neurodegeneration
  • plasma proteomics
  • vascular damage
  • sex related difference


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