Identification of circulating proteins associated with general cognitive function among middle-aged and older adults.
Communications biology 2023 ; 6: 1117.
Tin A, Fohner AE, Yang Q, Brody JA, Davies G, Yao J, Liu D, Caro I, Lindbohm JV, Duggan MR, Meirelles O, Harris SE, Gudmundsdottir V, Taylor AM, Henry A, Beiser AS, Shojaie A, Coors A, Fitzpatrick AL, Langenberg C, Satizabal CL, Sitlani CM, Wheeler E, Tucker-Drob EM, Bressler J, Coresh J, Bis JC, Candia J, Jennings LL, Pietzner M, Lathrop M, Lopez OL, Redmond P, Gerszten RE, Rich SS, Heckbert SR, Austin TR, Hughes TM, Tanaka T, Emilsson V, Vasan RS, Guo X, Zhu Y, Tzourio C, Rotter JI, Walker KA, Ferrucci L, Kivimaki M, Breteler MMB, Cox SR, Debette S, Mosley TH, Gudnason VG, Launer LJ, Psaty BM, Seshadri S, Fornage M
DOI : 10.1038/s42003-023-05454-1
PubMed ID : 37923804
PMCID : PMC10624811
URL : https://www.nature.com/articles/s42003-023-05454-1
Abstract
Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.