28 Sep 21. Featured Paper

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

Link to paper on Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring

Authors

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

Abstract

Introduction: This study aims to first discover plasma proteomic biomarkers relating to neurodegeneration (N) & vascular (V) damage in cognitively normal individuals & second to discover proteins mediating sex-related difference in N & V pathology.

Methods: Five thousand & thirty-two plasma proteins were measured in 1061 cognitively normal individuals (628 females & 433 males), nearly 90% of whom had magnetic resonance imaging measures of hippocampal volume (as N) & white matter hyperintensities (as V).

Results: Differential protein expression analysis & co-expression network analysis revealed different proteins & modules associated with N & V, respectively. Furthermore, causal mediation analysis revealed four proteins mediated sex-related difference in N & one protein mediated such difference in V damage.

Discussion: Once validated, the identified proteins could help to select cognitively normal individuals with N & V pathology for Alzheimer's disease clinical trials & provide targets for further mechanistic studies on brain sex differences, leading to sex-specific therapeutic strategies.

Keywords

• Mediation
• Neurodegeneration
• Plasma proteomics
• Sex-related difference
• Vascular damage