Organ aging signatures in the plasma proteome track health and disease

Nature, Journal Year: 2023, Volume and Issue: 624(7990), P. 164 - 172

Published: Dec. 6, 2023

Abstract Animal studies show aging varies between individuals as well organs within an individual 1–4 , but whether this is true in humans and its effect on age-related diseases unknown. We utilized levels of human blood plasma proteins originating from specific to measure organ-specific differences living individuals. Using machine learning models, we analysed 11 major estimated organ age reproducibly five independent cohorts encompassing 5,676 adults across the lifespan. discovered nearly 20% population strongly accelerated one 1.7% are multi-organ agers. Accelerated confers 20–50% higher mortality risk, relate faster those organs. find with heart have a 250% increased failure risk brain vascular predict Alzheimer’s disease (AD) progression independently pTau-181 (ref. 5 ), current best blood-based biomarker for AD. Our models link calcification, extracellular matrix alterations synaptic protein shedding early cognitive decline. introduce simple interpretable method study using proteomics data, predicting effects.

Language: Английский

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NULISA: a proteomic liquid biopsy platform with attomolar sensitivity and high multiplexing

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: Nov. 9, 2023

The blood proteome holds great promise for precision medicine but poses substantial challenges due to the low abundance of most plasma proteins and vast dynamic range proteome. Here we address these with NUcleic acid Linked Immuno-Sandwich Assay (NULISA™), which improves sensitivity traditional proximity ligation assays by ~10,000-fold attomolar level, suppressing assay background via a dual capture release mechanism built into oligonucleotide-conjugated antibodies. Highly multiplexed quantification both low- high-abundance spanning wide is achieved attenuating signals from abundant targets unconjugated antibodies next-generation sequencing barcoded reporter DNA. A 200-plex NULISA containing 124 cytokines chemokines other demonstrates superior extension in detecting biologically important low-abundance biomarkers patients autoimmune diseases COVID-19. Fully automated makes broad in-depth proteomic analysis easily accessible research diagnostic applications.

Language: Английский

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Proteomic analysis of Alzheimer’s disease cerebrospinal fluid reveals alterations associated with APOE ε4 and atomoxetine treatment

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(753)

Published: June 26, 2024

Alzheimer’s disease (AD) is currently defined by the aggregation of amyloid-β (Aβ) and tau proteins in brain. Although biofluid biomarkers are available to measure Aβ pathology, few markers complex pathophysiology that associated with these two cardinal neuropathologies. Here, we characterized proteomic landscape cerebrospinal fluid (CSF) changes pathology 300 individuals using different technologies—tandem mass tag spectrometry SomaScan. Integration both data types allowed for generation a robust protein coexpression network consisting 34 modules derived from 5242 measurements, including disease-relevant autophagy, ubiquitination, endocytosis, glycolysis. Three strongly apolipoprotein E ε4 ( APOE ε4) AD risk genotype mapped oxidant detoxification, mitogen-associated kinase signaling, neddylation, mitochondrial biology overlapped previously described lipoprotein module serum. Alterations all three blood were dementia more than 20 years before diagnosis. Analysis CSF samples an phase 2 clinical trial atomoxetine (ATX) demonstrated abnormal elevations glycolysis module—the most correlated cognitive function—were reduced ATX treatment. Clustering based on their profiles revealed heterogeneity pathological not fully reflected tau.

Language: Английский

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Comparative studies of 2168 plasma proteins measured by two affinity-based platforms in 4000 Chinese adults

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 21, 2025

Abstract Proteomics offers unique insights into human biology and drug development, but few studies have directly compared the utility of different proteomics platforms. We measured plasma levels 2168 proteins in 3976 Chinese adults using both Olink Explore SomaScan The correlation protein between platforms was modest (median rho = 0.29), with abundance data quality parameters being key factors influencing correlation. For 1694 one-to-one matched reagents, 765 513 had cis -pQTLs, including 400 colocalising -pQTLs. Moreover, 1096 1429 were associated BMI, while 279 154 risk ischaemic heart disease, respectively. Addition to conventional for disease improved C-statistics from 0.845 0.862 (NRI: 12.2%) 0.863 16.4%), These results demonstrate these could inform design interpretation future studies.

Language: Английский

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The application of Aptamer in biomarker discovery

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: July 19, 2023

Abstract Biomarkers are detectable molecules that can reflect specific physiological states of cells, organs, and organisms therefore be regarded as indicators for diseases. And the discovery biomarkers plays an essential role in cancer management from initial diagnosis to final treatment regime. Practically, reliable clinical still limited, restricted by suboptimal methods biomarker discovery. Nucleic acid aptamers nowadays could used a powerful tool protein biomarkers. single-strand oligonucleotides specifically bind various targets with high affinity. As artificial ssDNA or RNA, possess unique advantages compared conventional antibodies. They flexible design, low immunogenicity, relative chemical/thermos stability, well modifying convenience. Several SELEX (Systematic Evolution Ligands Exponential Enrichment) based have been generated recently construct discovering new different cell locations. Secretome SELEX-based selection facilitate identification secreted The developed cell-SELEX unveil those presented on surface. tissue-SELEX target intracellular multiplexed detection technology, aptamer-based SOMAScan analyze thousands proteins single run. In this review, we will introduce principle workflow variations methods, including secretome SELEX, ADAPT, Cell-SELEX tissue SELEX. Another proteome analyzing tool, SOMAScan, also covered. second half how these accelerate diseases, cardiovascular neurodegenerative discussed.

Language: Английский

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Carotenoids in Health as Studied by Omics-Related Endpoints

Advances in Nutrition, Journal Year: 2023, Volume and Issue: 14(6), P. 1538 - 1578

Published: Sept. 9, 2023

Carotenoids have been associated with risk reduction for several chronic diseases, including the association of their dietary intake/circulating levels reduced incidence obesity, type 2 diabetes, certain types cancer, and even lower total mortality. In addition to some carotenoids constituting vitamin A precursors, they are implicated in potential antioxidant effects pathways related inflammation oxidative stress, transcription factors such as nuclear factor κB erythroid 2-related 2. metabolites may also interact receptors, mainly retinoic acid receptor/retinoid X receptor peroxisome proliferator-activated which play a role immune system cellular differentiation. Therefore, large number downstream targets likely influenced by carotenoids, but not limited genes proteins stress inflammation, antioxidation, differentiation processes. Furthermore, recent studies propose an between carotenoid intake gut microbiota. While all these endpoints could be individually assessed, more complete/integrative way determine multitude health-related aspects includes (multi)omics-related techniques, especially transcriptomics, proteomics, lipidomics, metabolomics, well metagenomics, measured variety biospecimens plasma, urine, stool, white blood cells, or other tissue extracts. this review, we highlight use omics technologies assess mammalian organisms models.

Language: Английский

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Accelerated Aging in Cancer Survivors: Cellular Senescence, Frailty, and Possible Opportunities for Interventions

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(6), P. 3319 - 3319

Published: March 14, 2024

The population of cancer survivors has markedly increased due to the rapid improvements in treatment. However, experience accelerated aging, which leads chronic diseases and other age-related conditions, such as frailty. Those conditions may persist years after diagnosis Cellular senescence, a hallmark is one mechanisms that contribute aging survivors. Several measures, including measures based on clinical markers biomarkers, have been proposed estimate process, some them shown associations with mortality frailty anti-aging interventions, lifestyle changes drugs, proposed. Future research, particularly large-scale studies, needed determine efficiency these interventions before considering their application clinics. This review focuses cellular senescence survivors, assessment process using high prevalence population, well possible opportunities for interventions. A deeper understanding will development effective strategies mitigate improve quality life.

Language: Английский

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Serum proteomics reveal APOE-ε4-dependent and APOE-ε4-independent protein signatures in Alzheimer’s disease

Nature Aging, Journal Year: 2024, Volume and Issue: 4(10), P. 1446 - 1464

Published: Aug. 21, 2024

A deeper understanding of the molecular processes underlying late-onset Alzheimer's disease (LOAD) could aid in biomarker and drug target discovery. Using high-throughput serum proteomics prospective population-based Age, Gene/Environment Susceptibility-Reykjavik Study (AGES) cohort 5,127 older Icelandic adults (mean age, 76.6 ± 5.6 years), we identified 303 proteins associated with incident LOAD over a median follow-up 12.8 years. Over 40% these were independently APOE-ε4 carrier status, implicated neuronal overlapped protein signatures brain cerebrospinal fluid. We 17 whose associations strongly dependent on mostly consistent Remarkably, four (TBCA, ARL2, S100A13 IRF6) downregulated by yet upregulated due to LOAD, finding replicated external cohorts possibly reflecting response onset. These findings highlight dysregulated pathways at preclinical stages including those both independent status.

Language: Английский

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A blood‐based multi‐pathway biomarker assay for early detection and staging of Alzheimer's disease across ethnic groups

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(3), P. 2000 - 2015

Published: Jan. 6, 2024

Abstract INTRODUCTION Existing blood‐based biomarkers for Alzheimer's disease (AD) mainly focus on its pathological features. However, studies associated with other biological processes a comprehensive evaluation of AD status are limited. METHODS We developed blood‐based, multiplex biomarker assay that measures the levels 21 proteins involved in multiple pathways. evaluated assay's performance classifying and indicating AD‐related endophenotypes three independent cohorts from Chinese or European‐descent populations. RESULTS The 21‐protein accurately classified (area under receiver operating characteristic curve [AUC] = 0.9407 to 0.9867) mild cognitive impairment (MCI; AUC 0.8434 0.8945) while also brain amyloid pathology. Moreover, simultaneously changes five individuals revealed ethnic‐specific dysregulations upon progression. DISCUSSION This study demonstrated utility multi‐pathway early screening staging AD, providing insights patient stratification precision medicine. Highlights authors disease. classifies AD/MCI indicates can assess activities processes. Ethnic‐specific were revealed.

Language: Английский

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Reference Materials for Improving Reliability of Multiomics Profiling

Phenomics, Journal Year: 2024, Volume and Issue: 4(5), P. 487 - 521

Published: March 6, 2024

Abstract High-throughput technologies for multiomics or molecular phenomics profiling have been extensively adopted in biomedical research and clinical applications, offering a more comprehensive understanding of biological processes diseases. Omics reference materials play pivotal role ensuring the accuracy, reliability, comparability laboratory measurements analyses. However, current application omics has revealed several issues, including inappropriate selection underutilization, leading to inconsistencies across laboratories. This review aims address these concerns by emphasizing importance well-characterized at each level omics, encompassing (epi-)genomics, transcriptomics, proteomics, metabolomics. By summarizing their characteristics, advantages, limitations along with appropriate performance metrics pertinent study purposes, we provide an overview how can enhance data quality integration, thus fostering robust scientific investigations technologies.

Language: Английский

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