Plasma GDF15 affects long-term dementia risk and alters neuro-immune signaling.

Growth/differentiation factor-15 (GDF15) is a secreted peptide hormone and cytokine that is strongly associated with dementia risk. However, the extent to which plasma GDF15 represents a biomarker and driver of dementia risk remains unclear. Across multiple cohorts, we demonstrated that plasma GDF15 is associated with greater dementia risk over 15-to 25-year follow-up periods when measured in midlife, with stronger associations observed for vascular dementia compared to Alzheimer's disease (AD).

Serum Metabolomic Changes Following Bariatric Surgery Adjusted for Measured Glomerular Filtration Rate Suggest Mechanisms of Kidney Protection.

Background: Bariatric surgery reduces glomerular hyperfiltration in the short term and is associated with a reduced risk of glomerular filtration rate decline during long-term follow-up. Assessing surgery-induced changes in serum metabolites may be useful to understand the metabolic benefits to the kidney occurring after bariatric surgery.

Methods: In a prospective, single-center research cohort of 27 adults with severe obesity who underwent bariatric surgery, we measured serum metabolites using untargeted ultrahigh performance liquid chromatography-tandem mass spectrometry and measured glomerular filtration rate (mGFR) by iohexol plasma clearance 1-3 months prior and 6 months after bariatric surgery.

Proteomic signatures of corona and herpes viral antibodies identify IGDCC4 as a mediator of neurodegeneration.

Mechanisms underlying the dynamic relationships of viral infections and neurodegeneration warrant examination. Using a community-based cohort of older adults, the current study characterized the neurocognitive (cognitive functioning, brain volumes, Alzheimer's disease positron emission tomography, and plasma biomarkers) and plasma proteomic (7268 proteins) profiles of four common coronavirus and six herpesvirus antibody titers. Genetic inference techniques demonstrated the associations between viral antibody titers and neurocognitive outcomes may be attributed to altered expression in a subset of mechanistically relevant proteins in plasma.

Plant-Based Diets and Cardiovascular Events: A Proteomics Approach to Examine the Underlying Pathways.

Background: Plant-based diets are associated with a lower risk of cardiovascular disease (CVD). Proteomics may improve our understanding of the biological pathways underlying these associations.

Objectives: Using large-scale proteomics, we aimed to examine if plant-based diet-related proteins, which have been previously identified, are associated with incident CVD and subtypes of CVD in the Atherosclerosis Risk in Communities (ARIC) Study and Framingham Heart Study (FHS) Offspring cohort.

Serum and urine metabolite correlates of vitamin D supplementation in the Atherosclerosis Risk in Communities (ARIC) study.

Background & Aims: Vitamin D regulates calcium and phosphorus homeostasis, skeletal health, and potentially other aspects of health. There are limitations of existing vitamin D biomarkers. We aimed to discover novel vitamin D biomarkers by investigating serum and urine metabolites associated with vitamin D supplementation.

Correlations Within and Between Highly Multiplexed Proteomic Assays of Human Plasma.

Introduction: The number of assays on proteomic platforms has grown rapidly. The leading platforms, SomaScan and Olink, have strengths and limitations. Comparisons of precision on the latest platforms-SomaScan 11k and Olink Explore HT-have not yet been established.

Plasma Proteins Associated with the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) Diet and Incident Dementia.

Background: The Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet slows cognitive decline and protects brain health, but the mechanisms are poorly understood.

Objectives: We aimed to determine the plasma proteins associated with the MIND diet score and their ability to predict incident dementia in the Atherosclerosis Risk in Communities study.

Methods: We analyzed 10,230 Black and White participants at visit 3 (1993-1995) with food frequency questionnaire and proteomics data and randomly divided them into discovery (n = 6850) and replication (n = 3380) samples.

Proteomic Correlates of Vitamin D Supplementation in the Atherosclerosis Risk in Communities (ARIC) Study.

Purpose: Proteins are key effectors of biological functions and play roles in signaling, transport, growth, repair, and immunity. Vitamin D biomarkers may be reflected in the plasma proteome. The aim of this discovery study was to identify novel proteins associated with vitamin D supplementation.

Serum Metabolomic Markers of Dietary Potassium and Risk of CKD.

Key Points: We identified metabolomic markers of dietary potassium and diet-related metabolites that were associated with incident CKD in US adults. These metabolites may be prioritized for elucidating mechanisms that could be modified by dietary strategies to prevent CKD.

Background: Discovering metabolomic markers of dietary potassium may help improve dietary assessment of potassium and trace the effect of dietary potassium on CKD development.

Cross-Ancestry Comparison of Aptamer and Antibody Proteomics Measures.

Measures from affinity-proteomics platforms often correlate poorly, challenging interpretation of protein associations with genetic variants (pQTL) and phenotypes. Here, we examined 2,157 proteins measured on both SomaScan 7k and Olink Explore 3072 across 1,930 participants with genetic similarity to European, African, East Asian, and Admixed American ancestry references. Inter-platform correlation coefficients for these 2,157 proteins followed a bimodal distribution (median r=0.

Plasma proteomic characterization of motoric cognitive risk and mild cognitive impairment.

Introduction: Motoric cognitive risk (MCR) is a pre-dementia syndrome characterized by mobility and cognitive dysfunction. This study conducted a proteome-wide study of MCR and compared the proteomic signatures of MCR to that of mild cognitive impairment (MCI).

Methods: Participants were classified as MCR using a memory questionnaire and 4-meter walk.

Plasma Proteomic Signatures of Adiposity Are Associated With Cardiovascular Risk Factors and Type 2 Diabetes Risk in a Multiethnic Asian Population.

Unlabelled: The biomarkers connecting obesity and cardiometabolic diseases are not fully understood. We aimed to 1) evaluate the associations between BMI, waist circumference (WC), and ∼5,000 plasma proteins (SomaScan V4), 2) identify protein signatures of BMI and WC, and 3) evaluate the associations between the protein signatures and cardiometabolic health, including metabolically unhealthy obesity and type 2 diabetes incidence in the Singapore Multi-Ethnic Cohort Phase 1 (MEC1). Among 410 BMI-associated and 385 WC-associated proteins, we identified protein signatures of BMI and WC and validated them in an independent data set across two time points and externally in the Atherosclerosis Risk in Communities (ARIC) study.

Plasma proteome-wide analysis of cerebral small vessel disease identifies novel biomarkers and disease pathways.

Cerebral small vessel disease (SVD), as defined by neuroimaging characteristics such as white matter hyperintensities (WMHs), cerebral microhemorrhages (CMHs), and lacunar infarcts, is highly prevalent and has been associated with dementia risk and other clinical sequelae. Although conditions such as hypertension are known to contribute to SVD, little is known about the diverse set of subclinical biological processes and molecular mediators that may also influence the development and progression of SVD. To better understand the mechanisms underlying SVD and to identify novel SVD biomarkers, we used a large-scale proteomic platform to relate 4,877 plasma proteins to MRI-defined SVD characteristics within 1,508 participants of the Atherosclerosis Risk in Communities (ARIC) Study cohort.

Protein Biomarkers of Ultra-Processed Food Consumption and Risk of Coronary Heart Disease, Chronic Kidney Disease, and All-Cause Mortality.

Background: There is a need to understand the underlying biological mechanisms through which ultra-processed foods negatively affect health. Proteomics offers a valuable tool with which to examine different aspects of ultra-processed foods and their impact on health.

Objectives: The aim of this study was to identify protein biomarkers of usual ultra-processed food consumption and assess their relation to the incidence of coronary heart disease (CHD), chronic kidney disease (CKD), and all-cause mortality risk.

Proteomics identifies potential immunological drivers of postinfection brain atrophy and cognitive decline.

Infections have been associated with the incidence of Alzheimer disease and related dementias, but the mechanisms responsible for these associations remain unclear. Using a multicohort approach, we found that influenza, viral, respiratory, and skin and subcutaneous infections were associated with increased long-term dementia risk. These infections were also associated with region-specific brain volume loss, most commonly in the temporal lobe.

Proteomic analyses reveal plasma EFEMP1 and CXCL12 as biomarkers and determinants of neurodegeneration.

Introduction: Plasma proteomic analyses of unique brain atrophy patterns may illuminate peripheral drivers of neurodegeneration and identify novel biomarkers for predicting clinically relevant outcomes.

Methods: We identified proteomic signatures associated with machine learning-derived aging- and Alzheimer's disease (AD) -related brain atrophy patterns in the Baltimore Longitudinal Study of Aging (n = 815). Using data from five cohorts, we examined whether candidate proteins were associated with AD endophenotypes and long-term dementia risk.

Plasma proteomic comparisons change as coverage expands for SomaLogic and Olink.

The number of assays on highly-multiplexed proteomic platforms has grown tenfold over the past 15 years from less than 1,000 to >11,000. The leading aptamer-based and antibody-based platforms have different strengths. For example, Eldjarn et al demonstrated that the aptamer-based SomaScan 5k (4,907 assays, assessed in the Icelandic 36K) and the antibody-based Olink Explore 3072 (2,931 assays, assessed in the UK BioBank) had a similar number of -pQTLs among all targets (2,120 vs.

Plasma proteins associated with plant-based diets: Results from the Atherosclerosis Risk in Communities (ARIC) study and Framingham Heart Study (FHS).

Background & Aims: Plant-based diets are associated with a lower risk of chronic diseases. Large-scale proteomics can identify objective biomarkers of plant-based diets, and improve our understanding of the pathways that link plant-based diets to health outcomes. This study investigated the plasma proteome of four different plant-based diets [overall plant-based diet (PDI), provegetarian diet, healthful plant-based diet (hPDI), and unhealthful plant-based diet (uPDI)] in the Atherosclerosis Risk in Communities (ARIC) Study and replicated the findings in the Framingham Heart Study (FHS) Offspring cohort.

Proteome-wide analysis identifies plasma immune regulators of amyloid-beta progression.

While immune function is known to play a mechanistic role in Alzheimer's disease (AD), whether immune proteins in peripheral circulation influence the rate of amyloid-β (Aβ) progression - a central feature of AD - remains unknown. In the Baltimore Longitudinal Study of Aging, we quantified 942 immunological proteins in plasma and identified 32 (including CAT [catalase], CD36 [CD36 antigen], and KRT19 [keratin 19]) associated with rates of cortical Aβ accumulation measured with positron emission tomography (PET). Longitudinal changes in a subset of candidate proteins also predicted Aβ progression, and the mid- to late-life (20-year) trajectory of one protein, CAT, was associated with late-life Aβ-positive status in the Atherosclerosis Risk in Communities (ARIC) study.

Consistency of metabolite associations with measured glomerular filtration rate in children and adults.

Background: There is interest in identifying novel filtration markers that lead to more accurate GFR estimates than current markers (creatinine and cystatin C) and are more consistent across demographic groups. We hypothesize that large-scale metabolomics can identify serum metabolites that are strongly influenced by glomerular filtration rate (GFR) and are more consistent across demographic variables than creatinine, which would be promising filtration markers for future investigation.

Methods: We evaluated the consistency of associations between measured GFR (mGFR) and 887 common, known metabolites quantified by an untargeted chromatography- and spectroscopy-based metabolomics platform (Metabolon) performed on frozen blood samples from 580 participants in Chronic Kidney Disease in Children (CKiD), 674 participants in Modification of Diet in Renal Disease (MDRD) Study and 962 participants in African American Study of Kidney Disease and Hypertension (AASK).

Serum Metabolomic Markers of Protein-Rich Foods and Incident CKD: Results From the Atherosclerosis Risk in Communities Study.

Rationale & Objective: While urine excretion of nitrogen estimates the total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of 6 protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD).

Study Design: Prospective cohort study.

Plasma Metabolomics of Dietary Intake of Protein-Rich Foods and Kidney Disease Progression in Children.

Objective: Evidence regarding the efficacy of a low-protein diet for patients with CKD is inconsistent and recommending a low-protein diet for pediatric patients is controversial. There is also a lack of objective biomarkers of dietary intake. The purpose of this study was to identify plasma metabolites associated with dietary intake of protein and to assess whether protein-related metabolites are associated with CKD progression.

Plasma Biomarkers and Incident CKD Among Individuals Without Diabetes.

Rationale & Objective: Biomarkers of kidney disease progression have been identified in individuals with diabetes and underlying chronic kidney disease (CKD). Whether or not these markers are associated with the development of CKD in a general population without diabetes or CKD is not well established.

Study Design: Prospective observational cohort.