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Matthias Arnold

Adjunct Associate Professor in the Department of Psychiatry and Behavioral Sciences
Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences
2400 Pratt Street, North Pavilion, 7th Floor, Room # 7018, Durham, NC 27705

Selected Publications


Metabolomics profiling reveals distinct, sex-specific signatures in serum and brain metabolomes in mouse models of Alzheimer's disease.

Journal Article Alzheimers Dement · April 27, 2024 INTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation. METHODS: We investigat ... Full text Link to item Cite

Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer's disease.

Journal Article Sci Rep · March 13, 2024 In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and co ... Full text Link to item Cite

Serum Bile Acids Improve Prediction of Alzheimer's Progression in a Sex-Dependent Manner.

Journal Article Adv Sci (Weinh) · March 2024 Sex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes in serum BAs and AD development remains elusive. Here, authors quantitatively determined 33 serum BAs an ... Full text Link to item Cite

Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort.

Journal Article medRxiv · February 15, 2024 BACKGROUND: Acylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Studies linking AC levels to depression are few and provide mixed findings. We examined the association of circulating ACs l ... Full text Link to item Cite

Individual bioenergetic capacity as a potential source of resilience to Alzheimer's disease.

Journal Article medRxiv · January 24, 2024 Impaired glucose uptake in the brain is one of the earliest presymptomatic manifestations of Alzheimer's disease (AD). The absence of symptoms for extended periods of time suggests that compensatory metabolic mechanisms can provide resilience. Here, we int ... Full text Link to item Cite

New directions for Alzheimer's disease research from the Jackson Laboratory Center for Alzheimer's and Dementia Research 2022 workshop.

Journal Article Alzheimers Dement (N Y) · 2024 INTRODUCTION: In September 2022, The Jackson Laboratory Center for Alzheimer's and Dementia Research (JAX CADR) hosted a workshop with leading researchers in the Alzheimer's disease and related dementias (ADRD) field. METHODS: During the workshop, the part ... Full text Link to item Cite

Metabolomics profiling reveals distinct, sex-specific signatures in the serum and brain metabolomes in the mouse models of Alzheimer's disease.

Journal Article bioRxiv · December 22, 2023 INTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species provides a promising entry point for translation. ... Full text Link to item Cite

Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data.

Journal Article EBioMedicine · November 2023 BACKGROUND: Deep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. T ... Full text Link to item Cite

Plasma proteomic associations with genetics and health in the UK Biobank.

Journal Article Nature · October 2023 The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiative, including technical and biological validat ... Full text Link to item Cite

The Metabolome-Wide Signature of Major Depressive Disorder.

Journal Article Res Sq · September 21, 2023 Major Depressive Disorder (MDD) is an often-chronic condition with substantial molecular alterations and pathway dysregulations involved. Single metabolite, pathway and targeted metabolomics platforms have indeed revealed several metabolic alterations in d ... Full text Link to item Cite

Whole-body modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer's disease.

Journal Article Res Sq · September 6, 2023 In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and co ... Full text Link to item Cite

Cell-type-specific regulation of APOE and CLU levels in human neurons by the Alzheimer's disease risk gene SORL1.

Journal Article Cell Rep · August 29, 2023 SORL1 is implicated in the pathogenesis of Alzheimer's disease (AD) through genetic studies. To interrogate the roles of SORL1 in human brain cells, SORL1-null induced pluripotent stem cells (iPSCs) were differentiated to neuron, astrocyte, microglial, and ... Full text Link to item Cite

Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism.

Journal Article Sci Rep · August 23, 2023 Integration of the omics data, including metabolomics and proteomics, provides a unique opportunity to search for new associations within metabolic disorders, including Alzheimer's disease. Using metabolomics, we have previously profiled oxylipins, endocan ... Full text Link to item Cite

The HuMet Repository: Watching human metabolism at work.

Journal Article bioRxiv · August 9, 2023 The human metabolism constantly responds to stimuli such as food intake, fasting, exercise, and stress, triggering adaptive biochemical processes across multiple metabolic pathways. To understand the role of these processes and disruptions thereof in healt ... Full text Link to item Cite

Comparative brain metabolomics reveals shared and distinct metabolic alterations in Alzheimer's disease and progressive supranuclear palsy.

Journal Article medRxiv · July 27, 2023 Metabolic dysregulation is a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). While metabolic dysregulation is a common link between these two tauopathies, a comprehensive brain metabolic ... Full text Link to item Cite

Circulating lipid profiles are associated with cross-sectional and longitudinal changes of central biomarkers for Alzheimer's disease.

Journal Article medRxiv · June 21, 2023 Investigating the association of lipidome profiles with central Alzheimer's disease (AD) biomarkers, including amyloid/tau/neurodegeneration (A/T/N), can provide a holistic view between the lipidome and AD. We performed cross-sectional and longitudinal ass ... Full text Link to item Cite

Interplay of Metabolome and Gut Microbiome in Individuals With Major Depressive Disorder vs Control Individuals.

Journal Article JAMA Psychiatry · June 1, 2023 IMPORTANCE: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression. OBJECTIVE: To identify the metabolic signatures of maj ... Full text Link to item Cite

Differences and commonalities in the genetic architecture of protein quantitative trait loci in European and Arab populations.

Journal Article Hum Mol Genet · March 6, 2023 Polygenic scores (PGS) can identify individuals at risk of adverse health events and guide genetics-based personalized medicine. However, it is not clear how well PGS translate between different populations, limiting their application to well-studied ethni ... Full text Link to item Cite

Interplay of the human exposome, metabolome and gut microbiome in dementia and major depression

Journal Article Alzheimer's and Dementia · December 1, 2022 Background: The pathogenesis of dementia and depression is complex involving the interplay of genetic and environmental risk factors including diet, life-style and the gut microbiome. Dementia and depression co-occur and metabolomics studies may shed light ... Full text Cite

Interactions between brain and bile acid ratio profiles predict baseline cognitive status

Journal Article Alzheimer's and Dementia · December 1, 2022 Background: Alterations in the brain-gut microbiome system are thought to play an important role in the development of neurodegenerative diseases. While the great majority of secreted primary bile acids (BAs) are reabsorbed in the ileum, about 5% are metab ... Full text Cite

Metabolomics profiling reveals distinct, sex-specific signatures in serum and brain metabolomes in mouse models of Alzheimer's disease.

Journal Article Alzheimers Dement · April 27, 2024 INTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species can facilitate translation. METHODS: We investigat ... Full text Link to item Cite

Whole-body metabolic modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer's disease.

Journal Article Sci Rep · March 13, 2024 In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and co ... Full text Link to item Cite

Serum Bile Acids Improve Prediction of Alzheimer's Progression in a Sex-Dependent Manner.

Journal Article Adv Sci (Weinh) · March 2024 Sex disparities in serum bile acid (BA) levels and Alzheimer's disease (AD) prevalence have been established. However, the precise link between changes in serum BAs and AD development remains elusive. Here, authors quantitatively determined 33 serum BAs an ... Full text Link to item Cite

Acylcarnitines metabolism in depression: association with diagnostic status, depression severity and symptom profile in the NESDA cohort.

Journal Article medRxiv · February 15, 2024 BACKGROUND: Acylcarnitines (ACs) are involved in bioenergetics processes that may play a role in the pathophysiology of depression. Studies linking AC levels to depression are few and provide mixed findings. We examined the association of circulating ACs l ... Full text Link to item Cite

Individual bioenergetic capacity as a potential source of resilience to Alzheimer's disease.

Journal Article medRxiv · January 24, 2024 Impaired glucose uptake in the brain is one of the earliest presymptomatic manifestations of Alzheimer's disease (AD). The absence of symptoms for extended periods of time suggests that compensatory metabolic mechanisms can provide resilience. Here, we int ... Full text Link to item Cite

New directions for Alzheimer's disease research from the Jackson Laboratory Center for Alzheimer's and Dementia Research 2022 workshop.

Journal Article Alzheimers Dement (N Y) · 2024 INTRODUCTION: In September 2022, The Jackson Laboratory Center for Alzheimer's and Dementia Research (JAX CADR) hosted a workshop with leading researchers in the Alzheimer's disease and related dementias (ADRD) field. METHODS: During the workshop, the part ... Full text Link to item Cite

Metabolomics profiling reveals distinct, sex-specific signatures in the serum and brain metabolomes in the mouse models of Alzheimer's disease.

Journal Article bioRxiv · December 22, 2023 INTRODUCTION: Increasing evidence suggests that metabolic impairments contribute to early Alzheimer's disease (AD) mechanisms and subsequent dementia. Signals in metabolic pathways conserved across species provides a promising entry point for translation. ... Full text Link to item Cite

Circular-SWAT for deep learning based diagnostic classification of Alzheimer's disease: application to metabolome data.

Journal Article EBioMedicine · November 2023 BACKGROUND: Deep learning has shown potential in various scientific domains but faces challenges when applied to complex, high-dimensional multi-omics data. Alzheimer's Disease (AD) is a neurodegenerative disorder that lacks targeted therapeutic options. T ... Full text Link to item Cite

Plasma proteomic associations with genetics and health in the UK Biobank.

Journal Article Nature · October 2023 The Pharma Proteomics Project is a precompetitive biopharmaceutical consortium characterizing the plasma proteomic profiles of 54,219 UK Biobank participants. Here we provide a detailed summary of this initiative, including technical and biological validat ... Full text Link to item Cite

The Metabolome-Wide Signature of Major Depressive Disorder.

Journal Article Res Sq · September 21, 2023 Major Depressive Disorder (MDD) is an often-chronic condition with substantial molecular alterations and pathway dysregulations involved. Single metabolite, pathway and targeted metabolomics platforms have indeed revealed several metabolic alterations in d ... Full text Link to item Cite

Whole-body modelling reveals microbiome and genomic interactions on reduced urine formate levels in Alzheimer's disease.

Journal Article Res Sq · September 6, 2023 In this study, we aimed to understand the potential role of the gut microbiome in the development of Alzheimer's disease (AD). We took a multi-faceted approach to investigate this relationship. Urine metabolomics were examined in individuals with AD and co ... Full text Link to item Cite

Cell-type-specific regulation of APOE and CLU levels in human neurons by the Alzheimer's disease risk gene SORL1.

Journal Article Cell Rep · August 29, 2023 SORL1 is implicated in the pathogenesis of Alzheimer's disease (AD) through genetic studies. To interrogate the roles of SORL1 in human brain cells, SORL1-null induced pluripotent stem cells (iPSCs) were differentiated to neuron, astrocyte, microglial, and ... Full text Link to item Cite

Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism.

Journal Article Sci Rep · August 23, 2023 Integration of the omics data, including metabolomics and proteomics, provides a unique opportunity to search for new associations within metabolic disorders, including Alzheimer's disease. Using metabolomics, we have previously profiled oxylipins, endocan ... Full text Link to item Cite

The HuMet Repository: Watching human metabolism at work.

Journal Article bioRxiv · August 9, 2023 The human metabolism constantly responds to stimuli such as food intake, fasting, exercise, and stress, triggering adaptive biochemical processes across multiple metabolic pathways. To understand the role of these processes and disruptions thereof in healt ... Full text Link to item Cite

Comparative brain metabolomics reveals shared and distinct metabolic alterations in Alzheimer's disease and progressive supranuclear palsy.

Journal Article medRxiv · July 27, 2023 Metabolic dysregulation is a hallmark of neurodegenerative diseases, including Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). While metabolic dysregulation is a common link between these two tauopathies, a comprehensive brain metabolic ... Full text Link to item Cite

Circulating lipid profiles are associated with cross-sectional and longitudinal changes of central biomarkers for Alzheimer's disease.

Journal Article medRxiv · June 21, 2023 Investigating the association of lipidome profiles with central Alzheimer's disease (AD) biomarkers, including amyloid/tau/neurodegeneration (A/T/N), can provide a holistic view between the lipidome and AD. We performed cross-sectional and longitudinal ass ... Full text Link to item Cite

Interplay of Metabolome and Gut Microbiome in Individuals With Major Depressive Disorder vs Control Individuals.

Journal Article JAMA Psychiatry · June 1, 2023 IMPORTANCE: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression. OBJECTIVE: To identify the metabolic signatures of maj ... Full text Link to item Cite

Differences and commonalities in the genetic architecture of protein quantitative trait loci in European and Arab populations.

Journal Article Hum Mol Genet · March 6, 2023 Polygenic scores (PGS) can identify individuals at risk of adverse health events and guide genetics-based personalized medicine. However, it is not clear how well PGS translate between different populations, limiting their application to well-studied ethni ... Full text Link to item Cite

Interplay of the human exposome, metabolome and gut microbiome in dementia and major depression

Journal Article Alzheimer's and Dementia · December 1, 2022 Background: The pathogenesis of dementia and depression is complex involving the interplay of genetic and environmental risk factors including diet, life-style and the gut microbiome. Dementia and depression co-occur and metabolomics studies may shed light ... Full text Cite

Interactions between brain and bile acid ratio profiles predict baseline cognitive status

Journal Article Alzheimer's and Dementia · December 1, 2022 Background: Alterations in the brain-gut microbiome system are thought to play an important role in the development of neurodegenerative diseases. While the great majority of secreted primary bile acids (BAs) are reabsorbed in the ileum, about 5% are metab ... Full text Cite

APOE ε2 resilience for Alzheimer's disease is mediated by plasma lipid species: Analysis of three independent cohort studies.

Journal Article Alzheimers Dement · November 2022 INTRODUCTION: The apolipoprotein E (APOE) genotype is the strongest genetic risk factor for late-onset Alzheimer's disease. However, its effect on lipid metabolic pathways, and their mediating effect on disease risk, is poorly understood. METHODS: We perfo ... Full text Link to item Cite

Multi-Omic analyses characterize the ceramide/sphingomyelin pathway as a therapeutic target in Alzheimer's disease.

Journal Article Commun Biol · October 8, 2022 Dysregulation of sphingomyelin and ceramide metabolism have been implicated in Alzheimer's disease. Genome-wide and transcriptome-wide association studies have identified various genes and genetic variants in lipid metabolism that are associated with Alzhe ... Full text Link to item Cite

The landscape of metabolic brain alterations in Alzheimer's disease.

Journal Article Alzheimers Dement · July 13, 2022 INTRODUCTION: Alzheimer's disease (AD) is accompanied by metabolic alterations both in the periphery and the central nervous system. However, so far, a global view of AD-associated metabolic changes in the brain has been missing. METHODS: We metabolically ... Full text Link to item Cite

Genomics-based identification of a potential causal role for acylcarnitine metabolism in depression.

Journal Article J Affect Disord · June 15, 2022 BACKGROUND: Altered metabolism of acylcarnitines - transporting fatty acids to mitochondria - may link cellular energy dysfunction to depression. We examined the potential causal role of acylcarnitine metabolism in depression by leveraging genomics and Men ... Full text Link to item Cite

Comprehensive genetic analysis of the human lipidome identifies loci associated with lipid homeostasis with links to coronary artery disease.

Journal Article Nat Commun · June 6, 2022 We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species putatively in the mechanistic pathway for coronary artery disease (CAD). We quantified 596 lipid speci ... Full text Link to item Cite

Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer's disease.

Journal Article Alzheimers Dement · June 2022 Metabolites, the biochemical products of the cellular process, can be used to measure alterations in biochemical pathways related to the pathogenesis of Alzheimer's disease (AD). However, the relationships between systemic abnormalities in metabolism and t ... Full text Link to item Cite

Metabolomic and inflammatory signatures of symptom dimensions in major depression.

Journal Article Brain Behav Immun · May 2022 BACKGROUND: Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, energy-related symptoms bu ... Full text Link to item Cite

maplet: an extensible R toolbox for modular and reproducible metabolomics pipelines.

Journal Article Bioinformatics · January 27, 2022 UNLABELLED: This article presents maplet, an open-source R package for the creation of highly customizable, fully reproducible statistical pipelines for metabolomics data analysis. It builds on the SummarizedExperiment data structure to create a centralize ... Full text Link to item Cite

The metabolic landscape of brain alterations in Alzheimer's disease

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021 BACKGROUND: Impairment of brain glucose metabolism has been frequently described in Alzheimer's disease (AD). Moreover, the strongest predictor of the lifetime incidence of AD is the ε4 allele of APOE, a protein involved in lipid metabolism. These connecti ... Full text Cite

Investigating the importance of acylcarnitines in Alzheimer's disease

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021 BACKGROUND: L-carnitine is present in the mammalian cells as free carnitine (FC) and acylcarnitine and the adult human brain contains almost 10% of long chain acylcarnitine. Acylcarnitines are functionally involved in β-oxidation of fatty acids and are als ... Full text Cite

A proof of concept study towards multi-omics-based computational drug repositioning in Alzheimer's disease

Journal Article Alzheimer's & dementia : the journal of the Alzheimer's Association · December 1, 2021 BACKGROUND: Alzheimer's disease (AD) is a devastating neurodegenerative disorder for which there currently are no disease-modifying treatments available. To accelerate the path to effective intervention strategies, drug repositioning - the application of a ... Full text Cite

Mapping the proteo-genomic convergence of human diseases.

Journal Article Science · November 12, 2021 Characterization of the genetic regulation of proteins is essential for understanding disease etiology and developing therapies. We identified 10,674 genetic associations for 3892 plasma proteins to create a cis-anchored gene-protein-disease map of 1859 co ... Full text Link to item Cite

Genomics-based identification of a potential causal role for acylcarnitine metabolism in depression

Journal Article · October 19, 2021 ABSTRACTBackgroundAltered metabolism of acylcarnitines – transporting fatty acids to mitochondria – may link cellular energy dysfunction to depression. We examined the potential causal rol ... Full text Cite

Indoxyl sulfate, a gut microbiome-derived uremic toxin, is associated with psychic anxiety and its functional magnetic resonance imaging-based neurologic signature.

Journal Article Scientific reports · October 2021 It is unknown whether indoles, metabolites of tryptophan that are derived entirely from bacterial metabolism in the gut, are associated with symptoms of depression and anxiety. Serum samples (baseline, 12 weeks) were drawn from participants (n = 196) rando ... Full text Cite

Serum metabolomic biomarkers of perceptual speed in cognitively normal and mildly impaired subjects with fasting state stratification.

Journal Article Sci Rep · September 23, 2021 Cognitive decline is associated with both normal aging and early pathologies leading to dementia. Here we used quantitative profiling of metabolites involved in the regulation of inflammation, vascular function, neuronal function and energy metabolism, inc ... Full text Link to item Cite

Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression.

Journal Article Transl Psychiatry · March 2, 2021 Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomic ... Full text Open Access Link to item Cite

Multi-omics integration in biomedical research - A metabolomics-centric review.

Journal Article Anal Chim Acta · January 2, 2021 Recent advances in high-throughput technologies have enabled the profiling of multiple layers of a biological system, including DNA sequence data (genomics), RNA expression levels (transcriptomics), and metabolite levels (metabolomics). This has led to the ... Full text Link to item Cite

Serum metabolites associated with brain amyloid beta deposition, cognition and dementia progression.

Journal Article Brain Commun · 2021 Metabolomics in the Alzheimer's Disease Neuroimaging Initiative cohort provides a powerful tool for mapping biochemical changes in Alzheimer's disease, and a unique opportunity to learn about the association between circulating blood metabolites and brain ... Full text Link to item Cite

Comprehensive genetic analysis of the human lipidome identifies novel loci controlling lipid homeostasis with links to coronary artery disease

Journal Article · 2021 We integrated lipidomics and genomics to unravel the genetic architecture of lipid metabolism and identify genetic variants associated with lipid species that are putatively in the mechanistic pathway to coronary artery disease (CAD). We quantified 596 lip ... Full text Cite

Metabolomic and Inflammatory Signatures of Symptom Dimensions in Major Depression

Journal Article · 2021 ABSTRACTBackground Major depressive disorder (MDD) is a highly heterogenous disease, both in terms of clinical profiles and pathobiological alterations. Recently, immunometabolic dysregulations were shown to be correlated with atypical, ... Full text Cite

Multi-Omic Analyses Characterize the Ceramide/Sphingomyelin Pathway as a Therapeutic Target in Alzheimer’s Disease

Journal Article · 2021 Dysregulation of sphingomyelin (SM) and ceramide metabolism have been implicated in Alzheimer’s Disease (AD). Genome-wide and transcriptome wide association studies have identified various genes and genetic variants in lipid metabolism that are associated ... Full text Cite

An Integrated Molecular Atlas of Alzheimer’s Disease

Journal Article · 2021 ABSTRACTINTRODUCTION Embedding single-omics disease associations into the wider context of multi-level molecular changes in Alzheimer’s disease (AD) remains one central challenge in AD research. METHODSResults: from n ... Full text Cite

Metabolic Network Analysis Reveals Altered Bile Acid Synthesis and Metabolism in Alzheimer's Disease.

Journal Article Cell Rep Med · November 17, 2020 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 and identify genes in the alternative bile ... Full text Link to item Cite

Concordant peripheral lipidome signatures in two large clinical studies of Alzheimer's disease.

Journal Article Nat Commun · November 10, 2020 Changes to lipid metabolism are tightly associated with the onset and pathology of Alzheimer's disease (AD). Lipids are complex molecules comprising many isomeric and isobaric species, necessitating detailed analysis to enable interpretation of biological ... Full text Link to item Cite

Large eQTL meta-analysis reveals differing patterns between cerebral cortical and cerebellar brain regions.

Journal Article Sci Data · October 12, 2020 The availability of high-quality RNA-sequencing and genotyping data of post-mortem brain collections from consortia such as CommonMind Consortium (CMC) and the Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) Consortium enable the genera ... Full text Link to item Cite

Circulating ethanolamine plasmalogen indices in Alzheimer's disease: Relation to diagnosis, cognition, and CSF tau.

Journal Article Alzheimers Dement · September 2020 INTRODUCTION: Altered lipid metabolism is implicated in Alzheimer's disease (AD), but the mechanisms remain obscure. Aging-related declines in circulating plasmalogens containing omega-3 fatty acids may increase AD risk by reducing plasmalogen availability ... Full text Link to item Cite

Peripheral serum metabolomic profiles inform central cognitive impairment.

Journal Article Sci Rep · August 20, 2020 The incidence of Alzheimer's disease (AD) increases with age and is becoming a significant cause of worldwide morbidity and mortality. However, the metabolic perturbation behind the onset of AD remains unclear. In this study, we performed metabolite profil ... Full text Link to item Cite

Alzheimer's Risk Factors Age, APOE Genotype, and Sex Drive Distinct Molecular Pathways.

Journal Article Neuron · June 3, 2020 Evidence suggests interplay among the three major risk factors for Alzheimer's disease (AD): age, APOE genotype, and sex. Here, we present comprehensive datasets and analyses of brain transcriptomes and blood metabolomes from human apoE2-, apoE3-, and apoE ... Full text Link to item Cite

Serum triglycerides in Alzheimer disease: Relation to neuroimaging and CSF biomarkers.

Journal Article Neurology · May 19, 2020 OBJECTIVE: To investigate the association of triglyceride (TG) principal component scores with Alzheimer disease (AD) and the amyloid, tau, neurodegeneration, and cerebrovascular disease (A/T/N/V) biomarkers for AD. METHODS: Serum levels of 84 TG species w ... Full text Link to item Cite

Sex and APOE ε4 genotype modify the Alzheimer's disease serum metabolome.

Journal Article Nat Commun · March 2, 2020 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 metabolic differences. We systematically investigated group- ... Full text Link to item Cite

Acylcarnitine metabolomic profiles inform clinically-defined major depressive phenotypes.

Journal Article J Affect Disord · March 1, 2020 BACKGROUND: Acylcarnitines have important functions in mitochondrial energetics and β-oxidation, and have been implicated to play a significant role in metabolic functions of the brain. This retrospective study examined whether plasma acylcarnitine profile ... Full text Link to item Cite

Sets of coregulated serum lipids are associated with Alzheimer's disease pathophysiology.

Journal Article Alzheimers Dement (Amst) · December 2019 INTRODUCTION: Comorbidity with metabolic diseases indicates that lipid metabolism plays a role in the etiology of Alzheimer's disease (AD). Comprehensive lipidomic analysis can provide new insights into the altered lipid metabolism in AD. METHOD: In this s ... Full text Link to item Cite

Bile acids targeted metabolomics and medication classification data in the ADNI1 and ADNIGO/2 cohorts.

Journal Article Sci Data · October 17, 2019 Alzheimer's disease (AD) is the most common cause of dementia. The mechanism of disease development and progression is not well understood, but increasing evidence suggests multifactorial etiology, with a number of genetic, environmental, and aging-related ... Full text Link to item Cite

Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients.

Journal Article Transl Psychiatry · July 4, 2019 Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of ac ... Full text Open Access Link to item Cite

Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers.

Journal Article JAMA Netw Open · July 3, 2019 IMPORTANCE: Increasing evidence suggests an important role of liver function in the pathophysiology of Alzheimer disease (AD). The liver is a major metabolic hub; therefore, investigating the association of liver function with AD, cognition, neuroimaging, ... Full text Open Access Link to item Cite

Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers.

Journal Article Alzheimers Dement · February 2019 INTRODUCTION: Bile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer's disease (AD) including neuroinflammatio ... Full text Link to item Cite

Altered bile acid profile associates with cognitive impairment in Alzheimer's disease-An emerging role for gut microbiome.

Journal Article Alzheimers Dement · January 2019 INTRODUCTION: Increasing evidence suggests a role for the gut microbiome in central nervous system disorders and a specific role for the gut-brain axis in neurodegeneration. Bile acids (BAs), products of cholesterol metabolism and clearance, are produced i ... Full text Open Access Link to item Cite

PhenoDis: a comprehensive database for phenotypic characterization of rare cardiac diseases.

Journal Article Orphanet J Rare Dis · January 25, 2018 BACKGROUND: Thoroughly annotated data resources are a key requirement in phenotype dependent analysis and diagnosis of diseases in the area of precision medicine. Recent work has shown that curation and systematic annotation of human phenome data can signi ... Full text Link to item Cite

Brain and blood metabolite signatures of pathology and progression in Alzheimer disease: A targeted metabolomics study.

Journal Article PLoS Med · January 2018 BACKGROUND: The metabolic basis of Alzheimer disease (AD) is poorly understood, and the relationships between systemic abnormalities in metabolism and AD pathogenesis are unclear. Understanding how global perturbations in metabolism are related to severity ... Full text Link to item Cite

Targeted metabolomics and medication classification data from participants in the ADNI1 cohort.

Journal Article Scientific data · October 2017 Alzheimer's disease (AD) is the most common neurodegenerative disease presenting major health and economic challenges that continue to grow. Mechanisms of disease are poorly understood but significant data point to metabolic defects that might contribute t ... Full text Cite

Metabolic network failures in Alzheimer's disease: A biochemical road map.

Journal Article Alzheimers Dement · September 2017 INTRODUCTION: The Alzheimer's Disease Research Summits of 2012 and 2015 incorporated experts from academia, industry, and nonprofit organizations to develop new research directions to transform our understanding of Alzheimer's disease (AD) and propel the d ... Full text Link to item Cite

Connecting genetic risk to disease end points through the human blood plasma proteome.

Journal Article Nat Commun · February 27, 2017 Genome-wide association studies (GWAS) with intermediate phenotypes, like changes in metabolite and protein levels, provide functional evidence to map disease associations and translate them into clinical applications. However, although hundreds of genetic ... Full text Link to item Cite

Candidate gene variants of the immune system and sudden infant death syndrome.

Journal Article Int J Legal Med · July 2016 BACKGROUND: Sudden infant death syndrome (SIDS) causes early infant death with an incidence between 0.5 and 2.5 cases among 1000 live births. Besides central sleep apnea and thermal dysregulation, infections have been repeatedly suggested to be implicated ... Full text Link to item Cite

Genome-Wide Association Study with Targeted and Non-targeted NMR Metabolomics Identifies 15 Novel Loci of Urinary Human Metabolic Individuality.

Journal Article PLoS Genet · September 2015 Genome-wide association studies with metabolic traits (mGWAS) uncovered many genetic variants that influence human metabolism. These genetically influenced metabotypes (GIMs) contribute to our metabolic individuality, our capacity to respond to environment ... Full text Link to item Cite

SNiPA: an interactive, genetic variant-centered annotation browser.

Journal Article Bioinformatics · April 15, 2015 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 to heterogeneous data formats. T ... Full text Link to item Cite

An atlas of genetic influences on human blood metabolites.

Journal Article Nat Genet · June 2014 Genome-wide association scans with high-throughput metabolic profiling provide unprecedented insights into how genetic variation influences metabolism and complex disease. Here we report the most comprehensive exploration of genetic loci influencing human ... Full text Link to item Cite

Genome-wide association studies in asthma: what they really told us about pathogenesis.

Journal Article Curr Opin Allergy Clin Immunol · February 2013 PURPOSE OF REVIEW: Over the past years, several consortia have provided a data deluge from large-scale, genome-wide association studies (GWASs) for numerous asthma and allergy related traits. Dozens of reviews have already summarized the main results, alth ... Full text Link to item Cite

Network-based SNP meta-analysis identifies joint and disjoint genetic features across common human diseases.

Journal Article BMC Genomics · September 18, 2012 BACKGROUND: Genome-wide association studies (GWAS) have provided a large set of genetic loci influencing the risk for many common diseases. Association studies typically analyze one specific trait in single populations in an isolated fashion without taking ... Full text Link to item Cite

[Multicomponent therapy of fibromyalgia syndrome. Systematic review, meta-analysis and guideline].

Journal Article Schmerz · June 2012 BACKGROUND: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041 ... Full text Link to item Cite

Cis-acting polymorphisms affect complex traits through modifications of microRNA regulation pathways.

Journal Article PLoS One · 2012 Genome-wide association studies (GWAS) have become an effective tool to map genes and regions contributing to multifactorial human diseases and traits. A comparably small number of variants identified by GWAS are known to have a direct effect on protein st ... Full text Link to item Cite