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5. Opportunities and barriers in omics-based biomarker discovery for steatotic liver diseases

Author

Hansen, Torben, Mann, Matthias, Matthijnssens, Jelle, Krag, Aleksander, Bork, Peer, Arumugam, Manimozhiyan, Trebicka, Jonel, Karsdal, Morten, Anastasiadou, Ema, Israelsen, Hans, Melberg, Hans Olav, Legido-Quigley, Cristina, Thiele, Maja, Villesen, Ida Falk, Niu, Lili, Johansen, Stine, Sulek, Karolina, Nishijima, Suguru, Espen, Lore Van, Keller, Marisa, Israelsen, Mads, Suvitaival, Tommi, Zawadzki, Andressa de, Juel, Helene Bæk, Brol, Maximilian Joseph, Stinson, Sara Elizabeth, Huang, Yun, Silva, Maria Camilla Alvarez, Kuhn, Michael, Leeming, Diana Julie, Dalgaard, Louise Torp, and Jensen, Lars Juhl

Published
2024
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6. Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease

Author

Gómez-Pascual, Alicia, Naccache, Talel, Xu, Jin, Hooshmand, Kourosh, Wretlind, Asger, Gabrielli, Martina, Lombardo, Marta Tiffany, Shi, Liu, Buckley, Noel J., Tijms, Betty M., Vos, Stephanie J.B., ten Kate, Mara, Engelborghs, Sebastiaan, Sleegers, Kristel, Frisoni, Giovanni B., Wallin, Anders, Lleó, Alberto, Popp, Julius, Martinez-Lage, Pablo, Streffer, Johannes, Barkhof, Frederik, Zetterberg, Henrik, Visser, Pieter Jelle, Lovestone, Simon, Bertram, Lars, Nevado-Holgado, Alejo J., Gualerzi, Alice, Picciolini, Silvia, Proitsi, Petroula, Verderio, Claudia, Botía, Juan A., and Legido-Quigley, Cristina

Published
2024
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7. Infections increase the risk of decompensation and death in patients with early alcohol-related liver disease

Author

Anastasiadou, Ema, Arumugam, Manimozhian, Bork, Peer, Hansen, Torben, Presto, Jenny, Israelsen, Hans, Karsdal, Morten, Legido-Quigley, Cristina, Melberg, Hans Olav, Thiele, Maja, Trebicka, Jonel, Krag, Aleksander, Mann, Mathias, Matthijnssens, Jelle, Johansen, Stine, Langkjær, Simon, Rasmussen, Ditlev Nytoft, Israelsen, Mads, Torp, Nikolaj, Lindvig, Katrine, Kjærgaard, Maria, Hansen, Johanne Kragh, Hansen, Camilla Dalby, Thorhauge, Katrine, Andersen, Peter, Detlefsen, Sönke, Juel, Helene Bæk, and Justesen, Ulrik Stenz

Published
2024
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8. Multivariate GWAS of Alzheimer’s disease CSF biomarker profiles implies GRIN2D in synaptic functioning

Author

Neumann, Alexander, Ohlei, Olena, Küçükali, Fahri, Bos, Isabelle J., Timsina, Jigyasha, Vos, Stephanie, Prokopenko, Dmitry, Tijms, Betty M., Andreasson, Ulf, Blennow, Kaj, Vandenberghe, Rik, Scheltens, Philip, Teunissen, Charlotte E., Engelborghs, Sebastiaan, Frisoni, Giovanni B., Blin, Oliver, Richardson, Jill C., Bordet, Régis, Lleó, Alberto, Alcolea, Daniel, Popp, Julius, Marsh, Thomas W., Gorijala, Priyanka, Clark, Christopher, Peyratout, Gwendoline, Martinez-Lage, Pablo, Tainta, Mikel, Dobson, Richard J. B., Legido-Quigley, Cristina, Van Broeckhoven, Christine, Tanzi, Rudolph E., ten Kate, Mara, Lill, Christina M., Barkhof, Frederik, Cruchaga, Carlos, Lovestone, Simon, Streffer, Johannes, Zetterberg, Henrik, Visser, Pieter Jelle, Sleegers, Kristel, and Bertram, Lars

Published
2023
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10. Identification of biomarkers for glycaemic deterioration in type 2 diabetes

Author

Slieker, Roderick C., Donnelly, Louise A., Akalestou, Elina, Lopez-Noriega, Livia, Melhem, Rana, Güneş, Ayşim, Abou Azar, Frederic, Efanov, Alexander, Georgiadou, Eleni, Muniangi-Muhitu, Hermine, Sheikh, Mahsa, Giordano, Giuseppe N., Åkerlund, Mikael, Ahlqvist, Emma, Ali, Ashfaq, Banasik, Karina, Brunak, Søren, Barovic, Marko, Bouland, Gerard A., Burdet, Frédéric, Canouil, Mickaël, Dragan, Iulian, Elders, Petra J. M., Fernandez, Celine, Festa, Andreas, Fitipaldi, Hugo, Froguel, Phillippe, Gudmundsdottir, Valborg, Gudnason, Vilmundur, Gerl, Mathias J., van der Heijden, Amber A., Jennings, Lori L., Hansen, Michael K., Kim, Min, Leclerc, Isabelle, Klose, Christian, Kuznetsov, Dmitry, Mansour Aly, Dina, Mehl, Florence, Marek, Diana, Melander, Olle, Niknejad, Anne, Ottosson, Filip, Pavo, Imre, Duffin, Kevin, Syed, Samreen K., Shaw, Janice L., Cabrera, Over, Pullen, Timothy J., Simons, Kai, Solimena, Michele, Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Lim, Gareth E., Estall, Jennifer, Ibberson, Mark, Beulens, Joline W. J., ’t Hart, Leen M, Pearson, Ewan R., and Rutter, Guy A.

Published
2023
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11. Investigating associations between blood metabolites, later life brain imaging measures, and genetic risk for Alzheimer’s disease

Author

Green, Rebecca E., Lord, Jodie, Scelsi, Marzia A., Xu, Jin, Wong, Andrew, Naomi-James, Sarah, Handy, Alex, Gilchrist, Lachlan, Williams, Dylan M., Parker, Thomas D., Lane, Christopher A., Malone, Ian B., Cash, David M., Sudre, Carole H., Coath, William, Thomas, David L., Keuss, Sarah, Dobson, Richard, Legido-Quigley, Cristina, Fox, Nick C., Schott, Jonathan M., Richards, Marcus, and Proitsi, Petroula

Published
2023
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12. A combined DHA-rich fish oil and cocoa flavanols intervention does not improve cognition or brain structure in older adults with memory complaints: results from the CANN randomized, controlled parallel-design study

Author

Vauzour, David, Scholey, Andrew, White, David J, Cohen, Neal J, Cassidy, Aedín, Gillings, Rachel, Irvine, Michael A, Kay, Colin D, Kim, Min, King, Rebecca, Legido-Quigley, Cristina, Potter, John F, Schwarb, Hilary, and Minihane, Anne-Marie

Published
2023
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13. Rifaximin-α for liver fibrosis in patients with alcohol-related liver disease (GALA-RIF): a randomised, double-blind, placebo-controlled, phase 2 trial

Author

Anastasiadou, Ema, Arumugam, Manimozhian, Bork, Peer, Hansen, Torben, Henrar, Roland, Israelsen, Hans, Karsdal, Morten, Legido-Quigley, Cristina, Melberg, Hans Olav, Thiele, Maja, Trebicka, Jonel, Krag, Aleksander, Mann, Mathias, Matthijnssens, Jelle, Israelsen, Mads, Madsen, Bjørn Stæhr, Torp, Nikolaj, Johansen, Stine, Hansen, Camilla Dalby, Detlefsen, Sönke, Andersen, Peter, Hansen, Johanne Kragh, Lindvig, Katrine Prier, Rasmussen, Ditlev Nytoft, Thorhauge, Katrine Holtz, Kjærgaard, Maria, and Arumugam, Manimozhiyan

Published
2023
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14. Sphingolipids Are Depleted in Alcohol-Related Liver Fibrosis

Author

Bork, Peer, Mann, Mathias, Matthijnssens, Jelle, Krag, Aleksander, Hansen, Torben, Anastasiadou, Ema, Arumugam, Manimozhiyan, Henrar, Roland, Israelsen, Hans, Karsdal, Morten, Legido-Quigley, Cristina, Melberg, Hans Olav, Thiele, Maja, Trebicka, Jonel, Suvitaival, Tommi, Trošt, Kajetan, Kim, Min, de Zawadzki, Andressa, Kjaergaard, Maria, Rasmussen, Ditlev Nytoft, Lindvig, Katrine Prier, Israelsen, Mads, Detlefsen, Sönke, Andersen, Peter, Juel, Helene Bæk, Nielsen, Trine, Georgiou, Stella, Filippa, Vicky, Kuhn, Michael, Nishijima, Suguru, Moitinho-Silva, Lucas, and Rossing, Peter

Published
2023
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15. Rare variants in IFFO1, DTNB, NLRC3 and SLC22A10 associate with Alzheimer’s disease CSF profile of neuronal injury and inflammation

Author

Neumann, Alexander, Küçükali, Fahri, Bos, Isabelle, Vos, Stephanie J. B., Engelborghs, Sebastiaan, De Pooter, Tim, Joris, Geert, De Rijk, Peter, De Roeck, Ellen, Tsolaki, Magda, Verhey, Frans, Martinez-Lage, Pablo, Tainta, Mikel, Frisoni, Giovanni, Blin, Oliver, Richardson, Jill, Bordet, Régis, Scheltens, Philip, Popp, Julius, Peyratout, Gwendoline, Johannsen, Peter, Frölich, Lutz, Vandenberghe, Rik, Freund-Levi, Yvonne, Streffer, Johannes, Lovestone, Simon, Legido-Quigley, Cristina, ten Kate, Mara, Barkhof, Frederik, Strazisar, Mojca, Zetterberg, Henrik, Bertram, Lars, Visser, Pieter Jelle, van Broeckhoven, Christine, and Sleegers, Kristel

Published
2022
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20. Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes

Author

Rotbain Curovic, Viktor, primary, Sørland, Brede A, additional, Hansen, Tine W, additional, Jain, Siddhi Y, additional, Sulek, Karolina, additional, Mattila, Ismo Matias, additional, Frimodt-Moller, Marie, additional, Trost, Kajetan, additional, Legido-Quigley, Cristina, additional, Theilade, Simone, additional, Tofte, Nete, additional, Winther, Signe Abitz, additional, Hansen, Christian Stevns, additional, Rossing, Peter, additional, and Ahluwalia, Tarunveer S, additional

Published
2024
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21. Prognostic performance of 7 biomarkers compared to liver biopsy in early alcohol-related liver disease

Author

Anastasiadou, Ema, Arumugam, Manimozhian, Bork, Peer, Hansen, Torben, Hartoft, Christina, Israelsen, Hans, Karsdal, Morten, Legido-Quigley, Cristina, Melberg, Hans Olav, Thiele, Maja, Trebicka, Jonel, Krag, Aleksander, Mann, Mathias, Matthijnssens, Jelle, Rasmussen, Ditlev Nytoft, Johansen, Stine, Kjærgaard, Maria, Lindvig, Katrine Prier, Israelsen, Mads, Antonsen, Steen, and Detlefsen, Sönke

Published
2021
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23. Metabolic network failures in Alzheimer's disease: A biochemical road map

Author

Toledo, Jon B, Arnold, Matthias, Kastenmüller, Gabi, Chang, Rui, Baillie, Rebecca A, Han, Xianlin, Thambisetty, Madhav, Tenenbaum, Jessica D, Suhre, Karsten, Thompson, J Will, St. John‐Williams, Lisa, MahmoudianDehkordi, Siamak, Rotroff, Daniel M, Jack, John R, Motsinger‐Reif, Alison, Risacher, Shannon L, Blach, Colette, Lucas, Joseph E, Massaro, Tyler, Louie, Gregory, Zhu, Hongjie, Dallmann, Guido, Klavins, Kristaps, Koal, Therese, Kim, Sungeun, Nho, Kwangsik, Shen, Li, Casanova, Ramon, Varma, Sudhir, Legido‐Quigley, Cristina, Moseley, M Arthur, Zhu, Kuixi, Henrion, Marc YR, van der Lee, Sven J, Harms, Amy C, Demirkan, Ayse, Hankemeier, Thomas, van Duijn, Cornelia M, Trojanowski, John Q, Shaw, Leslie M, Saykin, Andrew J, Weiner, Michael W, Doraiswamy, P Murali, and Kaddurah‐Daouk, Rima

Subjects
Medical Biochemistry and Metabolomics, Biomedical and Clinical Sciences, Clinical Research, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), Neurodegenerative, Alzheimer's Disease, Acquired Cognitive Impairment, Aging, Dementia, Brain Disorders, Aetiology, 2.1 Biological and endogenous factors, Neurological, Aged, Aged, 80 and over, Alzheimer Disease, Amino Acids, Amyloid beta-Peptides, Aniline Compounds, Cognitive Dysfunction, Cohort Studies, Cross-Sectional Studies, Fasting, Female, Humans, Male, Metabolic Diseases, Metabolic Networks and Pathways, Metabolomics, Peptide Fragments, Phosphatidylcholines, Sphingomyelins, Thiazoles, tau Proteins, Metabonomics, Pharmacometabolomics, Pharmacometabonomics, Biomarkers, Serum, Metabolism, Systems biology, Biochemical networks, Precision medicine, Alzheimer's disease, Branched-chain amino acids, Phospholipids, Acylcarnitines, Alzheimer's Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium, Clinical Sciences, Geriatrics, Clinical sciences, Biological psychology
Abstract

IntroductionThe 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 development of critically needed therapies. In response to their recommendations, big data at multiple levels are being generated and integrated to study network failures in disease. We used metabolomics as a global biochemical approach to identify peripheral metabolic changes in AD patients and correlate them to cerebrospinal fluid pathology markers, imaging features, and cognitive performance.MethodsFasting serum samples from the Alzheimer's Disease Neuroimaging Initiative (199 control, 356 mild cognitive impairment, and 175 AD participants) were analyzed using the AbsoluteIDQ-p180 kit. Performance was validated in blinded replicates, and values were medication adjusted.ResultsMultivariable-adjusted analyses showed that sphingomyelins and ether-containing phosphatidylcholines were altered in preclinical biomarker-defined AD stages, whereas acylcarnitines and several amines, including the branched-chain amino acid valine and α-aminoadipic acid, changed in symptomatic stages. Several of the analytes showed consistent associations in the Rotterdam, Erasmus Rucphen Family, and Indiana Memory and Aging Studies. Partial correlation networks constructed for Aβ1-42, tau, imaging, and cognitive changes provided initial biochemical insights for disease-related processes. Coexpression networks interconnected key metabolic effectors of disease.DiscussionMetabolomics identified key disease-related metabolic changes and disease-progression-related changes. Defining metabolic changes during AD disease trajectory and its relationship to clinical phenotypes provides a powerful roadmap for drug and biomarker discovery.

Published
2017

24. Replication and cross-validation of type 2 diabetes subtypes based on clinical variables: an IMI-RHAPSODY study

Author

Slieker, Roderick C., Donnelly, Louise A., Fitipaldi, Hugo, Bouland, Gerard A., Giordano, Giuseppe N., Åkerlund, Mikael, Gerl, Mathias J., Ahlqvist, Emma, Ali, Ashfaq, Dragan, Iulian, Festa, Andreas, Hansen, Michael K., Mansour Aly, Dina, Kim, Min, Kuznetsov, Dmitry, Mehl, Florence, Klose, Christian, Simons, Kai, Pavo, Imre, Pullen, Timothy J., Suvitaival, Tommi, Wretlind, Asger, Rossing, Peter, Lyssenko, Valeriya, Legido-Quigley, Cristina, Groop, Leif, Thorens, Bernard, Franks, Paul W., Ibberson, Mark, Rutter, Guy A., Beulens, Joline W. J., ‘t Hart, Leen M., and Pearson, Ewan R.

Published
2021
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25. Multi-omics profiling of living human pancreatic islet donors reveals heterogeneous beta cell trajectories towards type 2 diabetes

Author

Wigger, Leonore, Barovic, Marko, Brunner, Andreas-David, Marzetta, Flavia, Schöniger, Eyke, Mehl, Florence, Kipke, Nicole, Friedland, Daniela, Burdet, Frederic, Kessler, Camille, Lesche, Mathias, Thorens, Bernard, Bonifacio, Ezio, Legido-Quigley, Cristina, Barbier Saint Hilaire, Pierre, Delerive, Philippe, Dahl, Andreas, Klose, Christian, Gerl, Mathias J., Simons, Kai, Aust, Daniela, Weitz, Jürgen, Distler, Marius, Schulte, Anke M., Mann, Matthias, Ibberson, Mark, and Solimena, Michele

Published
2021
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26. Paired plasma lipidomics and proteomics analysis in the conversion from mild cognitive impairment to Alzheimer's disease

Author

Gómez-Pascual, A, Naccache, T, Xu, J, Hooshmand, K, Wretlind, A, Gabrielli, M, Lombardo, M, Shi, L, Buckley, N, Tijms, B, Vos, S, Ten Kate, M, Engelborghs, S, Sleegers, K, Frisoni, G, Wallin, A, Lleó, A, Popp, J, Martinez-Lage, P, Streffer, J, Barkhof, F, Zetterberg, H, Visser, P, Lovestone, S, Bertram, L, Nevado-Holgado, A, Gualerzi, A, Picciolini, S, Proitsi, P, Verderio, C, Botía, J, Legido-Quigley, C, Gómez-Pascual, Alicia, Naccache, Talel, Xu, Jin, Hooshmand, Kourosh, Wretlind, Asger, Gabrielli, Martina, Lombardo, Marta Tiffany, Shi, Liu, Buckley, Noel J, Tijms, Betty M, Vos, Stephanie J B, Ten Kate, Mara, Engelborghs, Sebastiaan, Sleegers, Kristel, Frisoni, Giovanni B, Wallin, Anders, Lleó, Alberto, Popp, Julius, Martinez-Lage, Pablo, Streffer, Johannes, Barkhof, Frederik, Zetterberg, Henrik, Visser, Pieter Jelle, Lovestone, Simon, Bertram, Lars, Nevado-Holgado, Alejo J, Gualerzi, Alice, Picciolini, Silvia, Proitsi, Petroula, Verderio, Claudia, Botía, Juan A, Legido-Quigley, Cristina, Gómez-Pascual, A, Naccache, T, Xu, J, Hooshmand, K, Wretlind, A, Gabrielli, M, Lombardo, M, Shi, L, Buckley, N, Tijms, B, Vos, S, Ten Kate, M, Engelborghs, S, Sleegers, K, Frisoni, G, Wallin, A, Lleó, A, Popp, J, Martinez-Lage, P, Streffer, J, Barkhof, F, Zetterberg, H, Visser, P, Lovestone, S, Bertram, L, Nevado-Holgado, A, Gualerzi, A, Picciolini, S, Proitsi, P, Verderio, C, Botía, J, Legido-Quigley, C, Gómez-Pascual, Alicia, Naccache, Talel, Xu, Jin, Hooshmand, Kourosh, Wretlind, Asger, Gabrielli, Martina, Lombardo, Marta Tiffany, Shi, Liu, Buckley, Noel J, Tijms, Betty M, Vos, Stephanie J B, Ten Kate, Mara, Engelborghs, Sebastiaan, Sleegers, Kristel, Frisoni, Giovanni B, Wallin, Anders, Lleó, Alberto, Popp, Julius, Martinez-Lage, Pablo, Streffer, Johannes, Barkhof, Frederik, Zetterberg, Henrik, Visser, Pieter Jelle, Lovestone, Simon, Bertram, Lars, Nevado-Holgado, Alejo J, Gualerzi, Alice, Picciolini, Silvia, Proitsi, Petroula, Verderio, Claudia, Botía, Juan A, and Legido-Quigley, Cristina

Abstract

Background: Alzheimer's disease (AD) is a neurodegenerative condition for which there is currently no available medication that can stop its progression. Previous studies suggest that mild cognitive impairment (MCI) is a phase that precedes the disease. Therefore, a better understanding of the molecular mechanisms behind MCI conversion to AD is needed. Method: Here, we propose a machine learning-based approach to detect the key metabolites and proteins involved in MCI progression to AD using data from the European Medical Information Framework for Alzheimer's Disease Multimodal Biomarker Discovery Study. Proteins and metabolites were evaluated separately in multiclass models (controls, MCI and AD) and together in MCI conversion models (MCI stable vs converter). Only features selected as relevant by 3/4 algorithms proposed were kept for downstream analysis. Results: Multiclass models of metabolites highlighted nine features further validated in an independent cohort (0.726 mean balanced accuracy). Among these features, one metabolite, oleamide, was selected by all the algorithms. Further in-vitro experiments in rodents showed that disease-associated microglia excreted oleamide in vesicles. Multiclass models of proteins stood out with nine features, validated in an independent cohort (0.720 mean balanced accuracy). However, none of the proteins was selected by all the algorithms. Besides, to distinguish between MCI stable and converters, 14 key features were selected (0.872 AUC), including tTau, alpha-synuclein (SNCA), junctophilin-3 (JPH3), properdin (CFP) and peptidase inhibitor 15 (PI15) among others. Conclusions: This omics integration approach highlighted a set of molecules associated with MCI conversion important in neuronal and glia inflammation pathways.

Published
2024

27. Circulating metabolomic markers in association with overall burden of microvascular complications in type 1 diabetes

Author

Rotbain Curovic, Viktor, Sørland, Brede A., Hansen, Tine W., Jain, Siddhi Y., Sulek, Karolina, Mattila, Ismo Matias, Frimodt-Moller, Marie, Trost, Kajetan, Legido-Quigley, Cristina, Theilade, Simone, Tofte, Nete, Winther, Signe Abitz, Hansen, Christian Stevns, Rossing, Peter, Ahluwalia, Tarunveer S., Rotbain Curovic, Viktor, Sørland, Brede A., Hansen, Tine W., Jain, Siddhi Y., Sulek, Karolina, Mattila, Ismo Matias, Frimodt-Moller, Marie, Trost, Kajetan, Legido-Quigley, Cristina, Theilade, Simone, Tofte, Nete, Winther, Signe Abitz, Hansen, Christian Stevns, Rossing, Peter, and Ahluwalia, Tarunveer S.

Abstract

ntroduction Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality. Research design and methods In adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications—ie, presence of DKD±DR±DSPN) using linear regression models. Subsequently, the same metabolites were assessed with progression to endpoints: soft microvascular events (progression in albuminuria grade, ≥30% estimated glomerular filtration rate (eGFR) decline, or any progression in DR grade), hard microvascular events (progression to proliferative DR, chronic kidney failure, or ≥40% eGFR decline), and hard microvascular or macrovascular events (hard microvascular events, cardiovascular events (myocardial infarction, stroke, or arterial interventions), or cardiovascular mortality), using Cox models. All models were adjusted for sex, baseline age, diabetes duration, systolic blood pressure, HbA1c, body mass index, total cholesterol, smoking, and statin treatment. Results The full cohort investigated consisted of 487 participants. Mean (SD) follow-up was 4.8 (2.9, 5.7) years. Baseline biothesiometry was available in 202 participants, comprising the cross-sectional cohort. Eight metabolites were significantly associated with presence of DR, DKD, and DSPN, and six with additive microvascular burden severity. In the full cohort longitudinal analysis, higher levels of 3,4-dihydroxybutanoic acid (DHBA), 2,4-DHBA, ribonic acid, glycine, and ribitol were associated with development of events in both crude and adjusted models. Adding 3,4-DHBA, ribonic acid, and glycine to a traditional risk factor model improved the discrimination of hard micr, INTRODUCTION: Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality. RESEARCH DESIGN AND METHODS: In adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications-ie, presence of DKD±DR±DSPN) using linear regression models. Subsequently, the same metabolites were assessed with progression to endpoints: soft microvascular events (progression in albuminuria grade, ≥30% estimated glomerular filtration rate (eGFR) decline, or any progression in DR grade), hard microvascular events (progression to proliferative DR, chronic kidney failure, or ≥40% eGFR decline), and hard microvascular or macrovascular events (hard microvascular events, cardiovascular events (myocardial infarction, stroke, or arterial interventions), or cardiovascular mortality), using Cox models. All models were adjusted for sex, baseline age, diabetes duration, systolic blood pressure, HbA1c, body mass index, total cholesterol, smoking, and statin treatment. RESULTS: The full cohort investigated consisted of 487 participants. Mean (SD) follow-up was 4.8 (2.9, 5.7) years. Baseline biothesiometry was available in 202 participants, comprising the cross-sectional cohort. Eight metabolites were significantly associated with presence of DR, DKD, and DSPN, and six with additive microvascular burden severity. In the full cohort longitudinal analysis, higher levels of 3,4-dihydroxybutanoic acid (DHBA), 2,4-DHBA, ribonic acid, glycine, and ribitol were associated with development of events in both crude and adjusted models. Adding 3,4-DHBA, ribonic acid, and glycine to a traditional risk factor model improved the discrimination of hard microvascular e

Published
2024

28. Multi‐omics analysis reveals drivers of loss of β‐cell function after newly diagnosed autoimmune type 1 diabetes: An INNODIA multicenter study.

Author

Armenteros, Jose Juan Almagro, Brorsson, Caroline, Johansen, Christian Holm, Banasik, Karina, Mazzoni, Gianluca, Moulder, Robert, Hirvonen, Karoliina, Suomi, Tomi, Rasool, Omid, Bruggraber, Sylvaine F. A., Marcovecchio, M. Loredana, Hendricks, Emile, Al‐Sari, Naba, Mattila, Ismo, Legido‐Quigley, Cristina, Suvitaival, Tommi, Chmura, Piotr J., Knip, Mikael, Schulte, Anke M., and Lee, Jeong Heon

Subjects
TYPE 1 diabetes, MULTIOMICS, G protein coupled receptors, KILLER cells, GENETIC translation, AUTOIMMUNE diseases
Abstract

Aims: Heterogeneity in the rate of β‐cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease‐modifying clinical trials. Integrative analyses of baseline multi‐omics data obtained after the diagnosis of type 1 diabetes may provide mechanistic insight into the diverse rates of disease progression after type 1 diabetes diagnosis. Methods: We collected samples in a pan‐European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study, we used Multi‐Omics Factor Analysis to identify molecular signatures correlating with post‐diagnosis decline in β‐cell mass measured as fasting C‐peptide. Results: Two molecular signatures were significantly correlated with fasting C‐peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signalling, lymphoid and non‐lymphoid cell interactions and G‐protein coupled receptor signalling events that were inversely associated with a rapid decline in β‐cell function. The second signature was related to translation and viral infection was inversely associated with change in β‐cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid β‐cell decline. Conclusions: Features that differ between individuals with slow and rapid decline in β‐cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies as well as offering biomarkers of therapeutic effect. [ABSTRACT FROM AUTHOR]

Published
2024
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29. Review: Opportunities and barriers for omics-based biomarker discovery in steatotic liver diseases

Author

Thiele, Maja, primary, Villesen, Ida Falk, additional, Niu, Lili, additional, Johansen, Stine, additional, Sulek, Karolina, additional, Nishijima, Suguru, additional, Van Espen, Lore, additional, Keller, Marisa, additional, Israelsen, Mads, additional, Suvitaival, Tommi, additional, de Zawadzki, Andressa, additional, Juel, Helene Bæk, additional, Brol, Maximilian Joseph, additional, Stinson, Sara Elisabeth, additional, Huang, Yun, additional, Alvarez Silva, Maria Camilla, additional, Kuhn, Michael, additional, Anastasiadou, Ema, additional, Leeming, Diana Julie, additional, Karsdal, Morten, additional, Matthijnssens, Jelle, additional, Arumugam, Manimozhiyan, additional, Dalgaard, Louise Torp, additional, Legido-Quigley, Cristina, additional, Mann, Mathias, additional, Trebicka, Jonel, additional, Bork, Peer, additional, Jensen, Lars Juhl, additional, Hansen, Torben, additional, Krag, Aleksander, additional, Israelsen, Hans, additional, Melberg, Hans Olav, additional, Thiele, Maja, additional, and Mann, Matthias, additional

Published
2024
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30. Extracellular vesicles released by microglia and macrophages carry endocannabinoids which foster oligodendrocyte differentiation

Author

Lombardi, Marta, primary, Scaroni, Federica, additional, Gabrielli, Martina, additional, Raffaele, Stefano, additional, Bonfanti, Elisabetta, additional, Filipello, Fabia, additional, Giussani, Paola, additional, Picciolini, Silvia, additional, de Rosbo, Nicole Kerlero, additional, Uccelli, Antonio, additional, Golia, Maria Teresa, additional, D’Arrigo, Giulia, additional, Rubino, Tiziana, additional, Hooshmand, Kourosh, additional, Legido-Quigley, Cristina, additional, Fenoglio, Chiara, additional, Gualerzi, Alice, additional, Fumagalli, Marta, additional, and Verderio, Claudia, additional

Published
2024
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31. Infections Increase The Risk Of Decompensation And Death In Patients With Early Alcohol-Related Liver Disease

Author

Johansen, Stine, primary, Langkjær, Simon, additional, Rasmussen, Ditlev Nytoft, additional, Israelsen, Mads, additional, Torp, Nikolaj, additional, Lindvig, Katrine, additional, Kjærgaard, Maria, additional, Hansen, Johanne Kragh, additional, Hansen, Camilla Dalby, additional, Thorhauge, Katrine, additional, Andersen, Peter, additional, Detlefsen, Sönke, additional, Juel, Helene Bæk, additional, Justesen, Ulrik Stenz, additional, Hansen, Torben, additional, Krag, Aleksander, additional, Thiele, Maja, additional, Anastasiadou, Ema, additional, Arumugam, Manimozhian, additional, Bork, Peer, additional, Presto, Jenny, additional, Israelsen, Hans, additional, Karsdal, Morten, additional, Legido-Quigley, Cristina, additional, Melberg, Hans Olav, additional, Trebicka, Jonel, additional, Mann, Mathias, additional, and Matthijnssens, Jelle, additional

Published
2024
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36. Discovery and validation of plasma proteomic biomarkers relating to brain amyloid burden by SOMAscan assay

Author

Shi, Liu, Westwood, Sarah, Baird, Alison L., Winchester, Laura, Dobricic, Valerija, Kilpert, Fabian, Hong, Shengjun, Franke, Andre, Hye, Abdul, Ashton, Nicholas J., Morgan, Angharad R., Bos, Isabelle, Vos, Stephanie J.B., Buckley, Noel J., Kate, Mara ten, Scheltens, Philip, Vandenberghe, Rik, Gabel, Silvy, Meersmans, Karen, Engelborghs, Sebastiaan, De Roeck, Ellen E., Sleegers, Kristel, Frisoni, Giovanni B., Blin, Olivier, Richardson, Jill C., Bordet, Régis, Molinuevo, José L., Rami, Lorena, Wallin, Anders, Kettunen, Petronella, Tsolaki, Magda, Verhey, Frans, Lleó, Alberto, Alcolea, Daniel, Popp, Julius, Peyratout, Gwendoline, Martinez-Lage, Pablo, Tainta, Mikel, Johannsen, Peter, Teunissen, Charlotte E., Freund-Levi, Yvonne, Frölich, Lutz, Legido-Quigley, Cristina, Barkhof, Frederik, Blennow, Kaj, Zetterberg, Henrik, Baker, Susan, Morgan, B. Paul, Streffer, Johannes, Visser, Pieter Jelle, Bertram, Lars, Lovestone, Simon, and Nevado-Holgado, Alejo J.

Published
2019
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37. Inflammatory biomarkers in Alzheimer's disease plasma

Author

Bullmore, Edward T., Bhatti, Junaid, Chamberlain, Samuel J., Correia, Marta M., Crofts, Anna L., Dickinson, Amber, Foster, Andrew C., Kitzbichler, Manfred G., Knight, Clare, Lynall, Mary-Ellen, Maurice, Christina, O'Donnell, Ciara, Pointon, Linda J., St George Hyslop, Peter, Turner, Lorinda, Vertes, Petra, Widmer, Barry, Williams, Guy B., Morgan, B. Paul, Leckey, Claire A., Morgan, Angharad R., O'Hagan, Caroline, Touchard, Samuel, Cavanagh, Jonathan, Deith, Catherine, Farmer, Scott, McClean, John, McColl, Alison, McPherson, Andrew, Scouller, Paul, Sutherland, Murray, Boddeke, H.W.G.M., Richardson, Jill C., Khan, Shahid, Murphy, Phil, Parker, Christine A., Patel, Jai, Jones, Declan, de Boer, Peter, Kemp, John, Drevets, Wayne C., Nye, Jeffrey S., Wittenberg, Gayle, Isaac, John, Bhattacharya, Anindya, Carruthers, Nick, Kolb, Hartmuth, Pariante, Carmine M., Turkheimer, Federico, Barker, Gareth J., Byrom, Heidi, Cash, Diana, Cattaneo, Annamaria, Gee, Antony, Hastings, Caitlin, Mariani, Nicole, McLaughlin, Anna, Mondelli, Valeria, Nettis, Maria, Nikkheslat, Naghmeh, Randall, Karen, Sheridan, Hannah, Simmons, Camilla, Singh, Nisha, Van Loo, Victoria, Vicente-Rodriguez, Marta, Wood, Tobias C., Worrell, Courtney, Zajkowska, Zuzanna, Plath, Niels, Egebjerg, Jan, Eriksson, Hans, Gastambide, Francois, Adams, Karen Husted, Jeggo, Ross, Thomsen, Christian, Pederson, Jan Torleif, Campbell, Brian, Möller, Thomas, Nelson, Bob, Zorn, Stevin, O'Connor, Jason, Attenburrow, Mary Jane, Baird, Alison, Benjamin, Jithen, Clare, Stuart, Cowen, Philip, Huang, I-Shu (Dante), Hurley, Samuel, Jones, Helen, Lovestone, Simon, Mada, Francisca, Nevado-Holgado, Alejo, Oladejo, Akintayo, Ribe, Elena, Smith, Katy, Vyas, Anviti, Hughes, Zoe, Balice-Gordon, Rita, Duerr, James, Piro, Justin R., Sporn, Jonathan, Perry, V. Hugh, Cleal, Madeleine, Fryatt, Gemma, Gomez-Nicola, Diego, Mancuso, Renzo, Reynolds, Richard, Harrison, Neil A., Cercignani, Mara, Clarke, Charlotte L., Hoskins, Elizabeth, Kohn, Charmaine, Murray, Rosemary, Wilcock, Lauren, Wlazly, Dominika, Mount, Howard, Leckey, Claire, Nevado-Holgado, Alejo J., Barkhof, Frederik, Bertram, Lars, Blin, Olivier, Bos, Isabelle, Dobricic, Valerija, Engelborghs, Sebastiaan, Frisoni, Giovanni, Frölich, Lutz, Gabel, Silvey, Johannsen, Peter, Kettunen, Petronella, Kłoszewska, Iwona, Legido-Quigley, Cristina, Lleó, Alberto, Martinez-Lage, Pablo, Mecocci, Patrizia, Meersmans, Karen, Molinuevo, José Luis, Peyratout, Gwendoline, Popp, Julius, Richardson, Jill, Sala, Isabel, Scheltens, Philip, Streffer, Johannes, Soininen, Hikka, Tainta-Cuezva, Mikel, Teunissen, Charlotte, Tsolaki, Magda, Vandenberghe, Rik, Visser, Pieter Jelle, Vos, Stephanie, Wahlund, Lars-Olof, Wallin, Anders, Westwood, Sarah, and Zetterberg, Henrik

Published
2019
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38. Primary fatty amides in plasma associated with brain amyloid burden, hippocampal volume, and memory in the European Medical Information Framework for Alzheimer's Disease biomarker discovery cohort

Author

Kim, Min, Snowden, Stuart, Suvitaival, Tommi, Ali, Ashfaq, Merkler, David J., Ahmad, Tahmina, Westwood, Sarah, Baird, Alison, Proitsi, Petroula, Nevado-Holgado, Alejo, Hye, Abdul, Bos, Isabelle, Vos, Stephanie, Vandenberghe, Rik, Teunissen, Charlotte, ten Kate, Mara, Scheltens, Philip, Gabel, Silvy, Meersmans, Karen, Blin, Olivier, Richardson, Jill, De Roeck, Ellen, Sleegers, Kristel, Bordet, Régis, Rami, Lorena, Kettunen, Petronella, Tsolaki, Magda, Verhey, Frans, Sala, Isabel, Lléo, Alberto, Peyratout, Gwendoline, Tainta, Mikel, Johannsen, Peter, Freund-Levi, Yvonne, Frölich, Lutz, Dobricic, Valerija, Engelborghs, Sebastiaan, Frisoni, Giovanni B., Molinuevo, José L., Wallin, Anders, Popp, Julius, Martinez-Lage, Pablo, Bertram, Lars, Barkhof, Frederik, Ashton, Nicholas, Blennow, Kaj, Zetterberg, Henrik, Streffer, Johannes, Visser, Pieter J., Lovestone, Simon, and Legido-Quigley, Cristina

Published
2019
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39. Cerebrospinal fluid biomarkers of neurodegeneration, synaptic integrity, and astroglial activation across the clinical Alzheimer's disease spectrum

Author

Bos, Isabelle, Vos, Stephanie, Verhey, Frans, Scheltens, Philip, Teunissen, Charlotte, Engelborghs, Sebastiaan, Sleegers, Kristel, Frisoni, Giovanni, Blin, Olivier, Richardson, Jill C., Bordet, Régis, Tsolaki, Magda, Popp, Julius, Peyratout, Gwendoline, Martinez-Lage, Pablo, Tainta, Mikel, Lleó, Alberto, Johannsen, Peter, Freund-Levi, Yvonne, Frölich, Lutz, Vandenberghe, Rik, Westwood, Sarah, Dobricic, Valerija, Barkhof, Frederik, Legido-Quigley, Cristina, Bertram, Lars, Lovestone, Simon, Streffer, Johannes, Andreasson, Ulf, Blennow, Kaj, Zetterberg, Henrik, and Visser, Pieter Jelle

Published
2019
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43. Binge drinking episode causes acute, specific alterations in systemic and hepatic inflammation‐related markers

Author

Stankevic, Evelina, primary, Israelsen, Mads, additional, Juel, Helene Bæk, additional, Madsen, Anne Lundager, additional, Ängquist, Lars, additional, Aldiss, Peter Stuart Jacob, additional, Torp, Nikolaj, additional, Johansen, Stine, additional, Hansen, Camilla Dalby, additional, Hansen, Johanne Kragh, additional, Thorhauge, Katrine Holtz, additional, Lindvig, Katrine Prier, additional, Madsen, Bjørn Stæhr, additional, Sulek, Karolina, additional, Legido‐Quigley, Cristina, additional, Thiele, Maja Sofie, additional, Krag, Aleksander, additional, and Hansen, Torben, additional

Published
2023
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46. Urinary metabolic phenotyping for Alzheimer’s disease

Author

Kurbatova, Natalja, Garg, Manik, Whiley, Luke, Chekmeneva, Elena, Jiménez, Beatriz, Gómez-Romero, María, Pearce, Jake, Kimhofer, Torben, D’Hondt, Ellie, Soininen, Hilkka, Kłoszewska, Iwona, Mecocci, Patrizia, Tsolaki, Magda, Vellas, Bruno, Aarsland, Dag, Nevado-Holgado, Alejo, Liu, Benjamine, Snowden, Stuart, Proitsi, Petroula, Ashton, Nicholas J., Hye, Abdul, Legido-Quigley, Cristina, Lewis, Matthew R., Nicholson, Jeremy K., Holmes, Elaine, Brazma, Alvis, and Lovestone, Simon

Published
2020
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49. Rifaximin-α for liver fibrosis in patients with alcohol-related liver disease (GALA-RIF): a randomised, double-blind, placebo-controlled, phase 2 trial

Author

Israelsen, Mads, primary, Madsen, Bjørn Stæhr, additional, Torp, Nikolaj, additional, Johansen, Stine, additional, Hansen, Camilla Dalby, additional, Detlefsen, Sönke, additional, Andersen, Peter, additional, Hansen, Johanne Kragh, additional, Lindvig, Katrine Prier, additional, Rasmussen, Ditlev Nytoft, additional, Thorhauge, Katrine Holtz, additional, Kjærgaard, Maria, additional, Karsdal, Morten, additional, Hansen, Torben, additional, Arumugam, Manimozhiyan, additional, Trebicka, Jonel, additional, Thiele, Maja, additional, Krag, Aleksander, additional, Anastasiadou, Ema, additional, Arumugam, Manimozhian, additional, Bork, Peer, additional, Henrar, Roland, additional, Israelsen, Hans, additional, Legido-Quigley, Cristina, additional, Melberg, Hans Olav, additional, Mann, Mathias, additional, and Matthijnssens, Jelle, additional

Published
2023
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