PT - JOURNAL ARTICLE AU - Sarah E. Harris AU - Simon R. Cox AU - Steven Bell AU - Riccardo E. Marioni AU - Bram P Prins AU - Alison Pattie AU - Janie Corley AU - Susana Muñoz Maniega AU - Maria Valdés Hernández AU - Zoe Morris AU - Sally John AU - Paola G. Bronson AU - Elliot M. Tucker-Drob AU - John M. Starr AU - Mark E. Bastin AU - Joanna M. Wardlaw AU - Adam S Butterworth AU - Ian J. Deary TI - Neurology-related protein biomarkers are associated with general fluid cognitive ability and brain volume in older age AID - 10.1101/692459 DP - 2019 Jan 01 TA - bioRxiv PG - 692459 4099 - http://biorxiv.org/content/early/2019/07/04/692459.short 4100 - http://biorxiv.org/content/early/2019/07/04/692459.full AB - Identifying the biological correlates of late life cognitive function is important if we are to ascertain biomarkers for, and develop treatments to help reduce, age-related cognitive decline. This study investigated the associations between plasma levels of 91 neurology-related proteins (Olink® Proteomics) and general fluid cognitive ability in the Lothian Birth Cohort 1936 (LBC1936, N=798), the Lothian Birth Cohort 1921 (LBC1921, N=165), and the INTERVAL BioResource, (N=4,451). In LBC1936, we also examined mediation of protein-cognitive ability associations by MRI-derived indices of brain structure. In the LBC1936, 22 of the proteins and the first principal component (PC) created from a PC analysis of the 91 proteins, were associated with general fluid cognitive ability (β between −0.11 and −0.17, p<0.0029). Total brain volume partially mediated the association between 10 of these proteins and general fluid cognitive ability. Effect sizes for the 22 proteins, although smaller, were all in the same direction as in LBC1936 in an age-matched subsample of INTERVAL. Similar effect sizes were found for the majority of these 22 proteins in the older LBC1921. The associations were not replicated in a younger subset of INTERVAL. In conclusion, we identified plasma levels of a number of neurology-related proteins that were associated with general fluid cognitive ability in later life, some of which were mediated by brain volume.