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Identification of Candidate Biomarkers of Alzheimer’s Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics

Alzheimer’s disease (AD) is the most prevalent form of dementia among elderly people worldwide. Cerebrospinal fluid (CSF) is the optimal fluid source for AD biomarkers, while serum biomarkers are much more achievable. To search for novel diagnostic AD biomarkers, we performed a quantitative proteomi...

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Detalles Bibliográficos
Autores principales: Liu, Ping, Li, Lingxiao, He, Fangping, Meng, Fanxia, Liu, Xiaoyan, Su, Yujie, Su, Xinhui, Luo, Benyan, Peng, Guoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532410/
https://www.ncbi.nlm.nih.gov/pubmed/37762527
http://dx.doi.org/10.3390/ijms241814225
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author Liu, Ping
Li, Lingxiao
He, Fangping
Meng, Fanxia
Liu, Xiaoyan
Su, Yujie
Su, Xinhui
Luo, Benyan
Peng, Guoping
author_facet Liu, Ping
Li, Lingxiao
He, Fangping
Meng, Fanxia
Liu, Xiaoyan
Su, Yujie
Su, Xinhui
Luo, Benyan
Peng, Guoping
author_sort Liu, Ping
collection PubMed
description Alzheimer’s disease (AD) is the most prevalent form of dementia among elderly people worldwide. Cerebrospinal fluid (CSF) is the optimal fluid source for AD biomarkers, while serum biomarkers are much more achievable. To search for novel diagnostic AD biomarkers, we performed a quantitative proteomic analysis of CSF and serum samples from AD and normal cognitive controls (NC). CSF and serum proteomes were analyzed via data-independent acquisition quantitative mass spectrometry. Our bioinformatic analysis was based on Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. In comparison to the controls, 8 proteins were more abundant in AD CSF, and 60 were less abundant in AD CSF, whereas 55 proteins were more and 10 were less abundant in the serum samples. ATPase-associated activity for CSF and mitochondrial functions for CSF and serum were the most enriched GO terms of the DEPs. KEGG enrichment analysis showed that the most significant pathways for the differentially expressed proteins were the N-glycan biosynthesis pathways. The area under the curve (AUC) values for CSF sodium-/potassium-transporting ATPase subunit beta-1 (AT1B1), serglycin (SRGN), and thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) were 0.867 (p = 0.004), 0.833 (p = 0.008), and 0.783 (p = 0.025), respectively. A panel of the above three CSF proteins accurately differentiated AD (AUC = 0.933, p = 0.001) from NC. The AUC values for serum probable phospholipid-transporting ATPase IM (AT8B4) and SRGN were moderate. The AUC of the CSF SRGN + serum SRGN was 0.842 (p = 0.007). These novel AD biomarker candidates are mainly associated with inflammation, ATPase activity, oxidative stress, and mitochondrial dysfunction. Further studies are needed to investigate the molecular mechanisms by which these potential biomarkers are involved in AD.
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spelling pubmed-105324102023-09-28 Identification of Candidate Biomarkers of Alzheimer’s Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics Liu, Ping Li, Lingxiao He, Fangping Meng, Fanxia Liu, Xiaoyan Su, Yujie Su, Xinhui Luo, Benyan Peng, Guoping Int J Mol Sci Article Alzheimer’s disease (AD) is the most prevalent form of dementia among elderly people worldwide. Cerebrospinal fluid (CSF) is the optimal fluid source for AD biomarkers, while serum biomarkers are much more achievable. To search for novel diagnostic AD biomarkers, we performed a quantitative proteomic analysis of CSF and serum samples from AD and normal cognitive controls (NC). CSF and serum proteomes were analyzed via data-independent acquisition quantitative mass spectrometry. Our bioinformatic analysis was based on Gene Ontology (GO) functional annotation analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. In comparison to the controls, 8 proteins were more abundant in AD CSF, and 60 were less abundant in AD CSF, whereas 55 proteins were more and 10 were less abundant in the serum samples. ATPase-associated activity for CSF and mitochondrial functions for CSF and serum were the most enriched GO terms of the DEPs. KEGG enrichment analysis showed that the most significant pathways for the differentially expressed proteins were the N-glycan biosynthesis pathways. The area under the curve (AUC) values for CSF sodium-/potassium-transporting ATPase subunit beta-1 (AT1B1), serglycin (SRGN), and thioredoxin-dependent peroxide reductase, mitochondrial (PRDX3) were 0.867 (p = 0.004), 0.833 (p = 0.008), and 0.783 (p = 0.025), respectively. A panel of the above three CSF proteins accurately differentiated AD (AUC = 0.933, p = 0.001) from NC. The AUC values for serum probable phospholipid-transporting ATPase IM (AT8B4) and SRGN were moderate. The AUC of the CSF SRGN + serum SRGN was 0.842 (p = 0.007). These novel AD biomarker candidates are mainly associated with inflammation, ATPase activity, oxidative stress, and mitochondrial dysfunction. Further studies are needed to investigate the molecular mechanisms by which these potential biomarkers are involved in AD. MDPI 2023-09-18 /pmc/articles/PMC10532410/ /pubmed/37762527 http://dx.doi.org/10.3390/ijms241814225 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Liu, Ping
Li, Lingxiao
He, Fangping
Meng, Fanxia
Liu, Xiaoyan
Su, Yujie
Su, Xinhui
Luo, Benyan
Peng, Guoping
Identification of Candidate Biomarkers of Alzheimer’s Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics
title Identification of Candidate Biomarkers of Alzheimer’s Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics
title_full Identification of Candidate Biomarkers of Alzheimer’s Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics
title_fullStr Identification of Candidate Biomarkers of Alzheimer’s Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics
title_full_unstemmed Identification of Candidate Biomarkers of Alzheimer’s Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics
title_short Identification of Candidate Biomarkers of Alzheimer’s Disease via Multiplex Cerebrospinal Fluid and Serum Proteomics
title_sort identification of candidate biomarkers of alzheimer’s disease via multiplex cerebrospinal fluid and serum proteomics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10532410/
https://www.ncbi.nlm.nih.gov/pubmed/37762527
http://dx.doi.org/10.3390/ijms241814225
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