Matthias Arnold
A5075410200- Metabolomics and Mass Spectrometry Studies
- Alzheimer's disease research and treatments
- Diet and metabolism studies
- Tryptophan and brain disorders
- Bioinformatics and Genomic Networks
- Mitochondrial Function and Pathology
- Genetic Associations and Epidemiology
- Metabolism and Genetic Disorders
- Drug Transport and Resistance Mechanisms
- Liver Disease Diagnosis and Treatment
- Gut microbiota and health
- Adipose Tissue and Metabolism
- Peroxisome Proliferator-Activated Receptors
- Cholesterol and Lipid Metabolism
- Viral Infectious Diseases and Gene Expression in Insects
- Neuroinflammation and Neurodegeneration Mechanisms
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Folate and B Vitamins Research
- Innovative Microfluidic and Catalytic Techniques Innovation
- Computational Drug Discovery Methods
- Fatty Acid Research and Health
- Pharmacological Effects and Toxicity Studies
- Genomics and Rare Diseases
- Microbial Metabolic Engineering and Bioproduction
- Treatment of Major Depression
Duke University
2018-2025
Helmholtz Zentrum München
2016-2025
Institute of Bioinformatics and Systems Biology
2015-2024
Center for Environmental Health
2012-2024
Karlsruhe Institute of Technology
2024
GGZ inGeest
2024
Vrije Universiteit Amsterdam
2024
Amsterdam University Medical Centers
2024
Arkansas State University
2024
Emory University
2024
Abstract Genome-wide association studies (GWAS) with intermediate phenotypes, like changes in metabolite and protein levels, provide functional evidence to map disease associations translate them into clinical applications. However, although hundreds of genetic variants have been associated complex disorders, the underlying molecular pathways often remain elusive. Associations traits are key establishing links between GWAS-identified risk-variants end points. Here we describe a GWAS using...
Abstract Introduction Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and specific gut‐brain axis neurodegeneration. Bile acids (BAs), products of cholesterol metabolism clearance, are produced liver further metabolized by bacteria. They have major regulatory signaling functions seem dysregulated Alzheimer's disease (AD). Methods Serum levels 15 primary secondary BAs their conjugated forms were measured 1464 subjects including 370 cognitively...
The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide detailed summary this initiative, including technical and biological validations, insights into disease signatures, prediction modelling for various demographic health indicators. We present comprehensive protein quantitative trait locus (pQTL) mapping 2,923 proteins that identifies 14,287 primary genetic associations,...
Abstract Introduction The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, nonprofit organizations to develop new research directions transform our understanding disease (AD) propel the development critically needed therapies. In response their recommendations, big data at multiple levels are being generated integrated study network failures in disease. We used metabolomics as a global biochemical approach identify peripheral metabolic...
Background The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism AD pathogenesis are unclear. Understanding how global perturbations related to severity neuropathology eventual expression symptoms at-risk individuals critical developing effective disease-modifying treatments. In this study, we undertook parallel metabolomics analyses both brain blood identify correlates their associations with prodromal...
Detangling gene-disease connections Many diseases are at least partially due to genetic causes that not always understood or targetable with specific treatments. To provide insight into the biology of various human as well potential leads for therapeutic development, Pietzner et al . undertook detailed, genome-wide proteogenomic mapping. The authors analyzed thousands between disease-associated mutations, proteins, and medical conditions, thereby providing a detailed map use by future...
Abstract The availability of high-quality RNA-sequencing and genotyping data post-mortem brain collections from consortia such as CommonMind Consortium (CMC) the Accelerating Medicines Partnership for Alzheimer’s Disease (AMP-AD) enable generation a large-scale cis- eQTL meta-analysis. Here we generate cerebral cortical 1433 samples available four cohorts (identifying >4.1 million significant >18,000 genes), well cerebellar 261 874,836 >10,000 genes). We find substantially improved...
Abstract Motivation: Linking genes and functional information to genetic variants identified by association studies remains difficult. Resources containing extensive genomic annotations are available but often not fully utilized due heterogeneous data formats. To enhance their accessibility, we integrated many annotation datasets into a user-friendly webserver. Availability implementation: http://www.snipa.org/ Contact: g.kastenmueller@helmholtz-muenchen.de Supplementary information: at...
Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests microbiota influence pathological features Alzheimer's disease (AD) including neuroinflammation amyloid-β deposition.Serum levels 20 primary secondary BA metabolites from AD Neuroimaging Initiative (n = 1562) were measured using targeted metabolomic profiling. We assessed association BAs with "A/T/N" (amyloid, tau, neurodegeneration) biomarkers for AD:...
<h3>Importance</h3> Increasing evidence suggests an important role of liver function in the pathophysiology Alzheimer disease (AD). The is a major metabolic hub; therefore, investigating association with AD, cognition, neuroimaging, and CSF biomarkers would improve understanding dysfunction AD. <h3>Objective</h3> To examine whether markers are associated cognitive "A/T/N" (amyloid, tau, neurodegeneration) for <h3>Design, Setting, Participants</h3> In this cohort study, serum-based were...
Increasing evidence suggests Alzheimer's disease (AD) pathophysiology is influenced by primary and secondary bile acids, the end product of cholesterol metabolism. We analyze 2,114 post-mortem brain transcriptomes identify genes in alternative acid synthesis pathway to be expressed brain. A targeted metabolomic analysis acids measured from samples 111 individuals supports these results. Our metabolic network that taurine transport, synthesis, metabolism differ AD cognitively normal...
Late-onset Alzheimer's disease (AD) can, in part, be considered a metabolic disease. Besides age, female sex and APOE ε4 genotype represent strong risk factors for AD that also give rise to large differences. We systematically investigated group-specific alterations by conducting stratified association analyses of 139 serum metabolites 1,517 individuals from the Neuroimaging Initiative with biomarkers. observed substantial differences effects 15 partially overlapping status groups. Several...
Metabolites, the biochemical products of cellular process, can be used to measure alterations in pathways related pathogenesis Alzheimer's disease (AD). However, relationships between systemic abnormalities metabolism and AD are poorly understood. In this study, we aim identify AD-specific metabolomic changes their potential upstream genetic transcriptional regulators through an integrative systems biology framework for analyzing genetic, transcriptomic, metabolomic, proteomic data AD....
Importance Metabolomics reflect the net effect of genetic and environmental influences thus provide a comprehensive approach to evaluating pathogenesis complex diseases, such as depression. Objective To identify metabolic signatures major depressive disorder (MDD), elucidate direction associations using mendelian randomization, evaluate interplay human gut microbiome metabolome in development MDD. Design, Setting Participants This cohort study used data from participants UK Biobank (n = 500...
Abstract Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer’s disease (AD). Lipids complex molecules comprising many isomeric isobaric species, necessitating detailed analysis enable interpretation biological significance. Our expanded targeted lipidomics platform (569 species across 32 classes) allows for separation characterisation. In this study we examined peripheral samples two cohorts (AIBL, n = 1112 ADNI, 800). We able identify concordant...
Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our individuality, capacity respond environmental challenges, and susceptibility specific diseases. While homeostasis in blood is a well investigated topic large mGWAS over 150 known loci, detoxification through urinary excretion has only been addressed by few small 11 associated loci so far. Here we...
<h3>Objective</h3> To investigate the association of triglyceride (TG) principal component scores with Alzheimer disease (AD) and amyloid, tau, neurodegeneration, cerebrovascular (A/T/N/V) biomarkers for AD. <h3>Methods</h3> Serum levels 84 TG species were measured untargeted lipid profiling 689 participants from Alzheimer9s Disease Neuroimaging Initiative cohort, including 190 cognitively normal older adults (CN), 339 mild cognitive impairment (MCI), 160 Principal analysis factor rotation...
Abstract Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action not fully understood and therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing panel 180 metabolites to gain insights into response citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study...
Abstract It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, associated with symptoms depression and anxiety. Serum samples (baseline, 12 weeks) were drawn participants (n = 196) randomized to treatment cognitive behavioral therapy (CBT), escitalopram, or duloxetine for major depressive disorder. Baseline indoxyl sulfate abundance was positively correlated severity psychic anxiety total resting state functional connectivity...
Dysregulation of sphingomyelin and ceramide metabolism have been implicated in Alzheimer's disease. Genome-wide transcriptome-wide association studies identified various genes genetic variants lipid that are associated with However, the molecular mechanisms disruption remain to be determined. We focus on sphingolipid pathway carry out multi-omics analyses identify central peripheral metabolic changes patients, correlating them imaging features. Our approach is based (a) 2114 human...