Identification of plasma proteins relating to brain neurodegeneration and vascular pathology in cognitively normal individuals. Issue 1 (27th September 2021)

• Record Type: Journal Article
• Authors: 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.; Nevado‐Holgado, Alejo J.
• Is Part Of: Alzheimer's & dementia. Volume 13:Issue 1(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-27
• Subjects: mediation -- neurodegeneration -- plasma proteomics -- sex‐related difference -- vascular damage; Alzheimer's disease -- Periodicals; Alzheimer's disease -- Diagnosis -- Periodicals; Dementia -- Periodicals; Dementia -- Diagnosis -- Periodicals; 616.831
• DOI: 10.1002/dad2.12240
• Languages: English
• ISSNs: 2352-8729

Abstract

Abstract: Introduction: 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.