Identification of circulating proteins associated with general cognitive function among middle-aged and older adults

被引：8

作者：

Tin, Adrienne ^{[1
,2
,14
]}

Fohner, Alison E. ^{[3
,4
,5
]}

Yang, Qiong ^{[6
]}

Brody, Jennifer A. ^{[5
]}

Davies, Gail ^{[7
]}

Yao, Jie ^{[8
]}

Liu, Dan ^{[9
]}

Caro, Ilana ^{[10
]}

Lindbohm, Joni V. ^{[11
,12
,13
,14
]}

Duggan, Michael R. ^{[15
]}

Meirelles, Osorio ^{[16
]}

Harris, Sarah E. ^{[7
]}

Gudmundsdottir, Valborg ^{[17
,18
]}

Taylor, Adele M. ^{[7
]}

Henry, Albert ^{[19
]}

Beiser, Alexa S. ^{[6
,20
]}

Shojaie, Ali ^{[21
]}

Coors, Annabell ^{[9
]}

Fitzpatrick, Annette L. ^{[3
,22
]}

Langenberg, Claudia ^{[23
,24
,25
]}

Satizabal, Claudia L. ^{[20
,26
,27
,28
]}

Sitlani, Colleen M. ^{[5
]}

Wheeler, Eleanor ^{[24
]}

Tucker-Drob, Elliot M. ^{[29
]}

Bressler, Jan ^{[30
]}

Coresh, Josef ^{[31
]}

Bis, Joshua C. ^{[5
]}

Candia, Julian ^{[32
]}

Jennings, Lori L. ^{[33
]}

Pietzner, Maik ^{[23
,24
,25
]}

Lathrop, Mark ^{[34
]}

Lopez, Oscar L. ^{[35
,36
]}

Redmond, Paul ^{[7
]}

Gerszten, Robert E. ^{[37
]}

Rich, Stephen S. ^{[38
]}

Heckbert, Susan R. ^{[3
]}

Austin, Thomas R. ^{[3
,5
]}

Hughes, Timothy M. ^{[39
,40
]}

Tanaka, Toshiko ^{[32
]}

Emilsson, Valur ^{[17
,18
]}

Vasan, Ramachandran S. ^{[20
,41
,42
]}

Guo, Xiuqing ^{[8
]}

Zhu, Yineng ^{[6
]}

Tzourio, Christophe ^{[10
]}

Rotter, Jerome I. ^{[8
]}

Walker, Keenan A. ^{[15
]}

Ferrucci, Luigi ^{[32
]}

Kivimaki, Mika ^{[43
,44
]}

Breteler, Monique M. B. ^{[9
,45
]}

Cox, Simon R. ^{[7
]}

机构：

[1] Univ Mississippi, Med Ctr, MIND Ctr, Jackson, MS 39216 USA

[2] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA

[3] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[4] Univ Washington, Inst Publ Hlth Genet, Seattle, WA 98195 USA

[5] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[6] Boston Univ, Dept Biostat, Boston, MA USA

[7] Univ Edinburgh, Dept Psychol, Lothian Birth Cohorts, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland

[8] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Lundquist Inst Biomed Innovat, Dept Pediat, Torrance, CA USA

[9] German Ctr Neurodegenerat Dis DZNE, Populat Hlth Sci, Bonn, Germany

[10] Univ Bordeaux, INSERM, Bordeaux Populat Hlth Res Ctr, CHU Bordeaux,UMR 1219, Bordeaux, France

[11] MIT, Klarman Cell Observ, Broad Inst, Cambridge, MA USA

[12] Harvard Univ, Klarman Cell Observ, Broad Inst, Cambridge, MA USA

[13] Univ Helsinki, Dept Publ Hlth, Clinicum, Helsinki, Finland

[14] UCL, Dept Epidemiol & Publ Hlth, London, England

[15] NIA, Lab Behav Neurosci, Baltimore, MD USA

[16] NIA, NIH, Lab Epidemiol & Populat Sci, Bethesda, MD USA

[17] Univ Iceland, Fac Med, Reykjavik, Iceland

[18] Iceland Heart Assoc, Kopavogur, Iceland

[19] Univ London, Inst Cardiovasc Sci, London, England

[20] Framingham Heart Dis Epidemiol Study, Framingham, MA USA

[21] Univ Washington, Dept Biostat, Seattle, WA USA

[22] Univ Washington, Dept Family Med, Seattle, WA USA

[23] Queen Mary Univ London, Precis Healthcare Inst, London, England

[24] Univ Cambridge, MRC Epidemiol Unit, Cambridge, England

[25] Charite Univ Med Berlin, Berlin Inst Hlth, Computat Med, Berlin, Germany

[26] UT Hlth San Antonio, Dept Populat Hlth Sci, San Antonio, TX USA

[27] UT Hlth San Antonio, Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, San Antonio, TX USA

[28] Boston Univ, Dept Neurol, Sch Med, Boston, MA USA

[29] Univ Texas Austin, Dept Psychol, Austin, TX USA

[30] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA

[31] Johns Hopkins Univ, Baltimore, MD USA

[32] NIA, Translat Gerontol Branch, Baltimore, MD USA

[33] Novartis Inst Biomed Res, 22 Windsor St, Cambridge, MA USA

[34] McGill Genome Ctr, Montreal, PQ, Canada

[35] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA USA

[36] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA

[37] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA

[38] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Charlottesville, VA USA

[39] Wake Forest Sch Med, Dept Internal Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA

[40] Wake Forest Univ, Dept Epidemiol & Prevent, Sch Med, Winston Salem, NC USA

[41] Univ Texas Sch Publ Hlth San Antonio, San Antonio, TX USA

[42] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX USA

[43] UCL, UCL Brain Sci, London, England

[44] Univ Helsinki, Clinicum, Fac Med, Helsinki, Finland

[45] Univ Bonn, Fac Med, IMBIE, Bonn, Germany

[46] CHU Bordeaux, Dept Neurol, Inst Neurodegenerat Dis, Bordeaux, France

[47] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD USA

[48] Univ Washington, Dept Hlth Syst & Populat Hlth, Seattle, WA USA

[49] Univ Texas Hlth Sci Ctr Houston, McGovern Med Sch, Inst Mol Med, Houston, TX USA

来源：

COMMUNICATIONS BIOLOGY | 2023年 / 6卷 / 01期

基金：

美国国家卫生研究院; 英国生物技术与生命科学研究理事会;

关键词：

C-REACTIVE PROTEIN; GENOME-WIDE ASSOCIATION; MENDELIAN RANDOMIZATION; ALZHEIMERS-DISEASE; KIDNEY-FUNCTION; DEMENTIA; PLASMA; RISK; INSTRUMENTS; EXPRESSION;

D O I：

10.1038/s42003-023-05454-1

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. Analysis of circulating proteins across multiple cohorts identifies proteins that are associated with cognitive function and may serve as targets to understand the relationship between immunity and Alzheimer's disease risk.

引用

页数：14

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