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Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid-β and Incident Dementia

BACKGROUND: Plasma amyloid-β (Aβ) (Aβ(42), Aβ(40), and Aβ(42)/Aβ(40)), biomarkers of the Alzheimer’s form of dementia, are under consideration for clinical use. The associations of these peptides with circulating proteins may identify novel plasma biomarkers of dementia and inform peripheral factors...

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Autores principales: Tin, Adrienne, Sullivan, Kevin J., Walker, Keenan A., Bressler, Jan, Talluri, Rajesh, Yu, Bing, Simino, Jeanette, Gudmundsdottir, Valborg, Emilsson, Valur, Jennings, Lori L., Launer, Lenore, Mei, Hao, Boerwinkle, Eric, Windham, B. Gwen, Gottesman, Rebecca, Gudnason, Vilmundur, Coresh, Josef, Fornage, Myriam, Mosley, Thomas H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382706/
https://www.ncbi.nlm.nih.gov/pubmed/37519456
http://dx.doi.org/10.1016/j.bpsgos.2022.04.005
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author Tin, Adrienne
Sullivan, Kevin J.
Walker, Keenan A.
Bressler, Jan
Talluri, Rajesh
Yu, Bing
Simino, Jeanette
Gudmundsdottir, Valborg
Emilsson, Valur
Jennings, Lori L.
Launer, Lenore
Mei, Hao
Boerwinkle, Eric
Windham, B. Gwen
Gottesman, Rebecca
Gudnason, Vilmundur
Coresh, Josef
Fornage, Myriam
Mosley, Thomas H.
author_facet Tin, Adrienne
Sullivan, Kevin J.
Walker, Keenan A.
Bressler, Jan
Talluri, Rajesh
Yu, Bing
Simino, Jeanette
Gudmundsdottir, Valborg
Emilsson, Valur
Jennings, Lori L.
Launer, Lenore
Mei, Hao
Boerwinkle, Eric
Windham, B. Gwen
Gottesman, Rebecca
Gudnason, Vilmundur
Coresh, Josef
Fornage, Myriam
Mosley, Thomas H.
author_sort Tin, Adrienne
collection PubMed
description BACKGROUND: Plasma amyloid-β (Aβ) (Aβ(42), Aβ(40), and Aβ(42)/Aβ(40)), biomarkers of the Alzheimer’s form of dementia, are under consideration for clinical use. The associations of these peptides with circulating proteins may identify novel plasma biomarkers of dementia and inform peripheral factors influencing the levels of these peptides. METHODS: We analyzed the association of these 3 plasma Aβ measures with 4638 circulating proteins among a subset of the participants of the Atherosclerosis Risk in Communities (ARIC) study (midlife: n = 1955; late life: n = 2082), related the Aβ-associated proteins with incident dementia in the overall ARIC cohort (midlife: n = 11,069, late life: n = 4110) with external replication in the Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study (n = 4973), estimated the proportion of Aβ variance explained, and conducted enrichment analyses to characterize the proteins associated with the plasma Aβ peptides. RESULTS: At midlife, of the 296 Aβ-associated proteins, 8 were associated with incident dementia from midlife and late life in the ARIC study, and NPPB, IBSP, and THBS2 were replicated in the AGES–Reykjavik Study. At late life, of the 34 Aβ-associated proteins, none were associated with incident dementia at midlife, and kidney function explained 10%, 12%, and 0.2% of the variance of Aβ(42), Aβ(40), and Aβ(42)/Aβ(40), respectively. Aβ42-associated proteins at midlife were found to be enriched in the liver, and those at late life were found to be enriched in the spleen. CONCLUSIONS: This study identifies circulating proteins associated with plasma Aβ levels and incident dementia and informs peripheral factors associated with plasma Aβ levels.
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spelling pubmed-103827062023-07-30 Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid-β and Incident Dementia Tin, Adrienne Sullivan, Kevin J. Walker, Keenan A. Bressler, Jan Talluri, Rajesh Yu, Bing Simino, Jeanette Gudmundsdottir, Valborg Emilsson, Valur Jennings, Lori L. Launer, Lenore Mei, Hao Boerwinkle, Eric Windham, B. Gwen Gottesman, Rebecca Gudnason, Vilmundur Coresh, Josef Fornage, Myriam Mosley, Thomas H. Biol Psychiatry Glob Open Sci Archival Report BACKGROUND: Plasma amyloid-β (Aβ) (Aβ(42), Aβ(40), and Aβ(42)/Aβ(40)), biomarkers of the Alzheimer’s form of dementia, are under consideration for clinical use. The associations of these peptides with circulating proteins may identify novel plasma biomarkers of dementia and inform peripheral factors influencing the levels of these peptides. METHODS: We analyzed the association of these 3 plasma Aβ measures with 4638 circulating proteins among a subset of the participants of the Atherosclerosis Risk in Communities (ARIC) study (midlife: n = 1955; late life: n = 2082), related the Aβ-associated proteins with incident dementia in the overall ARIC cohort (midlife: n = 11,069, late life: n = 4110) with external replication in the Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study (n = 4973), estimated the proportion of Aβ variance explained, and conducted enrichment analyses to characterize the proteins associated with the plasma Aβ peptides. RESULTS: At midlife, of the 296 Aβ-associated proteins, 8 were associated with incident dementia from midlife and late life in the ARIC study, and NPPB, IBSP, and THBS2 were replicated in the AGES–Reykjavik Study. At late life, of the 34 Aβ-associated proteins, none were associated with incident dementia at midlife, and kidney function explained 10%, 12%, and 0.2% of the variance of Aβ(42), Aβ(40), and Aβ(42)/Aβ(40), respectively. Aβ42-associated proteins at midlife were found to be enriched in the liver, and those at late life were found to be enriched in the spleen. CONCLUSIONS: This study identifies circulating proteins associated with plasma Aβ levels and incident dementia and informs peripheral factors associated with plasma Aβ levels. Elsevier 2022-05-14 /pmc/articles/PMC10382706/ /pubmed/37519456 http://dx.doi.org/10.1016/j.bpsgos.2022.04.005 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Archival Report
Tin, Adrienne
Sullivan, Kevin J.
Walker, Keenan A.
Bressler, Jan
Talluri, Rajesh
Yu, Bing
Simino, Jeanette
Gudmundsdottir, Valborg
Emilsson, Valur
Jennings, Lori L.
Launer, Lenore
Mei, Hao
Boerwinkle, Eric
Windham, B. Gwen
Gottesman, Rebecca
Gudnason, Vilmundur
Coresh, Josef
Fornage, Myriam
Mosley, Thomas H.
Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid-β and Incident Dementia
title Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid-β and Incident Dementia
title_full Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid-β and Incident Dementia
title_fullStr Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid-β and Incident Dementia
title_full_unstemmed Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid-β and Incident Dementia
title_short Proteomic Analysis Identifies Circulating Proteins Associated With Plasma Amyloid-β and Incident Dementia
title_sort proteomic analysis identifies circulating proteins associated with plasma amyloid-β and incident dementia
topic Archival Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10382706/
https://www.ncbi.nlm.nih.gov/pubmed/37519456
http://dx.doi.org/10.1016/j.bpsgos.2022.04.005
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