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Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
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Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
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Journal Article
Proteomic landscape of Alzheimer’s Disease: novel insights into pathogenesis and biomarker discovery
2021
Overview
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.
Publisher
BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
Subject
/ Alzheimer Disease - etiology
/ Alzheimer Disease - genetics
/ Alzheimer Disease - metabolism
/ Analysis
/ Biomedical and Life Sciences
/ Cerebrospinal Fluid Proteins - analysis
/ Cognitive Dysfunction - metabolism
/ Dementia
/ Genes
/ Genomics
/ Humans
/ Ions
/ Labeling
/ Mutation
/ Nerve Tissue Proteins - analysis
/ Nerve Tissue Proteins - genetics
/ Nerve Tissue Proteins - metabolism
/ Peptides
/ Protein Processing, Post-Translational
/ Proteins
/ Proteome
/ PTM
/ Review
