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Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery

Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not onl...

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Autores principales: Bai, Bing, Vanderwall, David, Li, Yuxin, Wang, Xusheng, Poudel, Suresh, Wang, Hong, Dey, Kaushik Kumar, Chen, Ping-Chung, Yang, Ka, Peng, Junmin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359598/
https://www.ncbi.nlm.nih.gov/pubmed/34384464
http://dx.doi.org/10.1186/s13024-021-00474-z
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author Bai, Bing
Vanderwall, David
Li, Yuxin
Wang, Xusheng
Poudel, Suresh
Wang, Hong
Dey, Kaushik Kumar
Chen, Ping-Chung
Yang, Ka
Peng, Junmin
author_facet Bai, Bing
Vanderwall, David
Li, Yuxin
Wang, Xusheng
Poudel, Suresh
Wang, Hong
Dey, Kaushik Kumar
Chen, Ping-Chung
Yang, Ka
Peng, Junmin
author_sort Bai, Bing
collection PubMed
description Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not only validate canonical amyloid and tau pathways, but also uncover novel components in broad protein networks, such as RNA splicing, development, immunity, membrane transport, lipid metabolism, synaptic function, and mitochondrial activity. Meta-analysis of seven deep datasets reveals 2,698 differentially expressed (DE) proteins in the landscape of AD brain proteome (n = 12,017 proteins/genes), covering 35 reported AD genes and risk loci. The DE proteins contain cellular markers enriched in neurons, microglia, astrocytes, oligodendrocytes, and epithelial cells, supporting the involvement of diverse cell types in AD pathology. We discuss the hypothesized protective or detrimental roles of selected DE proteins, emphasizing top proteins in “amyloidome” (all biomolecules in amyloid plaques) and disease progression. Comprehensive PTM analysis represents another layer of molecular events in AD. In particular, tau PTMs are correlated with disease stages and indicate the heterogeneity of individual AD patients. Moreover, the unprecedented proteomic coverage of biofluids, such as cerebrospinal fluid and serum, procures novel putative AD biomarkers through meta-analysis. Thus, proteomics-driven systems biology presents a new frontier to link genotype, proteotype, and phenotype, accelerating the development of improved AD models and treatment strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13024-021-00474-z.
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spelling pubmed-83595982021-08-16 Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery Bai, Bing Vanderwall, David Li, Yuxin Wang, Xusheng Poudel, Suresh Wang, Hong Dey, Kaushik Kumar Chen, Ping-Chung Yang, Ka Peng, Junmin Mol Neurodegener Review Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD). Here we review the advances and limitations in historic and recent AD proteomic research. Complementary to genetic mapping, proteomic studies not only validate canonical amyloid and tau pathways, but also uncover novel components in broad protein networks, such as RNA splicing, development, immunity, membrane transport, lipid metabolism, synaptic function, and mitochondrial activity. Meta-analysis of seven deep datasets reveals 2,698 differentially expressed (DE) proteins in the landscape of AD brain proteome (n = 12,017 proteins/genes), covering 35 reported AD genes and risk loci. The DE proteins contain cellular markers enriched in neurons, microglia, astrocytes, oligodendrocytes, and epithelial cells, supporting the involvement of diverse cell types in AD pathology. We discuss the hypothesized protective or detrimental roles of selected DE proteins, emphasizing top proteins in “amyloidome” (all biomolecules in amyloid plaques) and disease progression. Comprehensive PTM analysis represents another layer of molecular events in AD. In particular, tau PTMs are correlated with disease stages and indicate the heterogeneity of individual AD patients. Moreover, the unprecedented proteomic coverage of biofluids, such as cerebrospinal fluid and serum, procures novel putative AD biomarkers through meta-analysis. Thus, proteomics-driven systems biology presents a new frontier to link genotype, proteotype, and phenotype, accelerating the development of improved AD models and treatment strategies. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13024-021-00474-z. BioMed Central 2021-08-12 /pmc/articles/PMC8359598/ /pubmed/34384464 http://dx.doi.org/10.1186/s13024-021-00474-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Review
Bai, Bing
Vanderwall, David
Li, Yuxin
Wang, Xusheng
Poudel, Suresh
Wang, Hong
Dey, Kaushik Kumar
Chen, Ping-Chung
Yang, Ka
Peng, Junmin
Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
title Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
title_full Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
title_fullStr Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
title_full_unstemmed Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
title_short Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
title_sort proteomic landscape of alzheimer’s disease: novel insights into pathogenesis and biomarker discovery
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359598/
https://www.ncbi.nlm.nih.gov/pubmed/34384464
http://dx.doi.org/10.1186/s13024-021-00474-z
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