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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Published inMolecular neurodegeneration Vol. 16; no. 1; pp. 55 - 16
Main Authors Bai, Bing, Vanderwall, David, Li, Yuxin, Wang, Xusheng, Poudel, Suresh, Wang, Hong, Dey, Kaushik Kumar, Chen, Ping-Chung, Yang, Ka, Peng, Junmin
Format Journal Article
LanguageEnglish
Published England BioMed Central Ltd 12.08.2021
BioMed Central
BMC
Subjects
Advertising executives
Alzheimer Disease - etiology
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer's disease
Amino acids
Analysis
Astrocytes
Asymptomatic Diseases
Biomarker
Biomarkers
Blood Proteins - analysis
Cerebrospinal fluid
Cerebrospinal Fluid Proteins - analysis
Chromatography, Liquid
Cognitive Dysfunction - metabolism
Data Mining
Databases, Protein
Datasets as Topic
Dementia
Development and progression
Epithelial cells
Gene mapping
Genes
Genomics
Genotypes
Humans
Hypotheses
Ions
Labeling
Lipid metabolism
Mass spectrometry
Mass spectroscopy
Meta-analysis
Meta-Analysis as Topic
Microglia
Mitochondria
Mutation
Nerve Tissue Proteins - analysis
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurodegeneration
Neurodegenerative diseases
Oligodendrocytes
Pathogenesis
Peptides
Phenotypes
Plaque, Amyloid - chemistry
Protein Processing, Post-Translational
Proteins
Proteome
Proteomes
Proteomics
Proteomics - methods
PTM
Review
Scientific imaging
Senile plaques
Tandem Mass Spectrometry
Tau protein
United States > US
Biomarker
Abeta
Alzheimer’s disease
Amyloidome
Pathogenesis
Proteomics
PTM
Proteome
Tau
Mass spectrometry
Online AccessGet full text

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Abstract 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.
AbstractList 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.
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.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.
Abstract 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.
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.
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. Keywords: Alzheimer's disease, Pathogenesis, Biomarker, Proteomics, Proteome, PTM, Mass spectrometry, Tau, Abeta, Amyloidome
ArticleNumber 55
Audience Academic
Author Yang, Ka
Bai, Bing
Poudel, Suresh
Wang, Xusheng
Li, Yuxin
Wang, Hong
Peng, Junmin
Dey, Kaushik Kumar
Vanderwall, David
Chen, Ping-Chung
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/34384464$$D View this record in MEDLINE/PubMed
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Issue 1
Keywords Biomarker
Abeta
Alzheimer’s disease
Amyloidome
Pathogenesis
Proteomics
PTM
Proteome
Tau
Mass spectrometry
Language English
License 2021. The Author(s).
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– reference: 34670601 - Mol Neurodegener. 2021 Oct 20;16(1):72. doi: 10.1186/s13024-021-00493-w
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Snippet Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD). Here we...
Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer's disease (AD). Here we...
Abstract Mass spectrometry-based proteomics empowers deep profiling of proteome and protein posttranslational modifications (PTMs) in Alzheimer’s disease (AD)....
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SubjectTerms Advertising executives
Alzheimer Disease - etiology
Alzheimer Disease - genetics
Alzheimer Disease - metabolism
Alzheimer's disease
Amino acids
Analysis
Astrocytes
Asymptomatic Diseases
Biomarker
Biomarkers
Blood Proteins - analysis
Cerebrospinal fluid
Cerebrospinal Fluid Proteins - analysis
Chromatography, Liquid
Cognitive Dysfunction - metabolism
Data Mining
Databases, Protein
Datasets as Topic
Dementia
Development and progression
Epithelial cells
Gene mapping
Genes
Genomics
Genotypes
Humans
Hypotheses
Ions
Labeling
Lipid metabolism
Mass spectrometry
Mass spectroscopy
Meta-analysis
Meta-Analysis as Topic
Microglia
Mitochondria
Mutation
Nerve Tissue Proteins - analysis
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurodegeneration
Neurodegenerative diseases
Oligodendrocytes
Pathogenesis
Peptides
Phenotypes
Plaque, Amyloid - chemistry
Protein Processing, Post-Translational
Proteins
Proteome
Proteomes
Proteomics
Proteomics - methods
PTM
Review
Scientific imaging
Senile plaques
Tandem Mass Spectrometry
Tau protein
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Title Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
URI https://www.ncbi.nlm.nih.gov/pubmed/34384464
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https://www.proquest.com/docview/2561488329
https://pubmed.ncbi.nlm.nih.gov/PMC8359598
https://doaj.org/article/d98af69a4ec9457ab6934693ca6ed550
Volume 16
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