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. 2020 Feb 10;11(1):800.
doi: 10.1038/s41467-019-14161-7.

Neurology-related protein biomarkers are associated with cognitive ability and brain volume in older age

Sarah E Harris  1   2 , Simon R Cox  3   4   5 , Steven Bell  6   7   8 , Riccardo E Marioni  3   9 , Bram P Prins  6 , Alison Pattie  4 , Janie Corley  3   4 , Susana Muñoz Maniega  3   10   11 , Maria Valdés Hernández  3   10   11 , Zoe Morris  10 , Sally John  12 , Paola G Bronson  12 , Elliot M Tucker-Drob  13 , John M Starr  3   14 , Mark E Bastin  3   5   10 , Joanna M Wardlaw  3   5   10   11 , Adam S Butterworth  6   7 , Ian J Deary  3   4
Affiliations

Neurology-related protein biomarkers are associated with cognitive ability and brain volume in older age

Sarah E Harris et al. Nat Commun. .

Abstract

Identifying 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. Here, we investigated the associations between plasma levels of 90 neurology-related proteins (Olink® Proteomics) and general fluid cognitive ability in the Lothian Birth Cohort 1936 (LBC1936, N = 798), Lothian Birth Cohort 1921 (LBC1921, N = 165), and the INTERVAL BioResource (N = 4451). In the LBC1936, 22 of the proteins were significantly associated with general fluid cognitive ability (β between -0.11 and -0.17). MRI-assessed total brain volume partially mediated the association between 10 of these proteins and general fluid cognitive ability. In an age-matched subsample of INTERVAL, effect sizes for the 22 proteins, although smaller, were all in the same direction as in LBC1936. Plasma levels of a number of neurology-related proteins are associated with general fluid cognitive ability in later life, mediated by brain volume in some cases.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. Principal component analysis on the 90 neurology-related proteins in INTERVAL-Young, INTERVAL-Old, LBC1936 and LBC1921.
a Heatmaps and b screenplots. Source data are provided as a Source Data file.
Fig. 2
Fig. 2. Heatmaps illustrating the loadings for individual proteins for the first three protein principal components for each cohort.
Heatmap illustrating the loadings for individual proteins for protein–PC1, PC2 and PC3 for INTERVAL-Young, INTERVAL-Old, LBC1936 and LBC1921.
Fig. 3
Fig. 3. Mediation analysis.
The association between EDA2R and gf was a significantly partially mediated (31%) by total brain volume in LBC1936. Indirect effect (a × b) = −0.048, p < 0.001. b Significantly partially mediated (36%) by brain MRI variables in LBC1936. Indirect effect (a × b) = −0.059, p < 0.001.
Fig. 4
Fig. 4. Mediation analysis in LBC1936 separated by brain variable.
Unique contributions from each of the brain variables are indicated with standard error bars. Gmvol = grey matter volume, NAWM vol = normal-appearing white matter volume, WMH vol = white matter hyperintensity volume, gFA = general fractional anisotropy, gMD = general mean diffusivity, PVS = perivascular spaces.
Fig. 5
Fig. 5. Regional distribution of protein–cortical associations.
a Corrected for age and sex, b corrected for age, sex, smoking status and antihypertensive medication use and the percentage attenuation due to the addition of smoking status and antihypertensive medication use. Source data are provided as a Source Data file.
See this image and copyright information in PMC

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