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1. Education as Risk Factor of Mild Cognitive Impairment: The Link to the Gut Microbiome

Author

Klee, Matthias, Aho, V. T. E., May, P., Heintz-Buschart, A., Landoulsi, Z., Jónsdóttir, S. R., Pauly, C., Pavelka, L., Delacour, L., Kaysen, A., Krüger, R., Wilmes, P., Leist, A. K., Acharya, Geeta, Aguayo, Gloria, Alexandre, Myriam, Ali, Muhammad, Ammerlann, Wim, Arena, Giuseppe, Bassis, Michele, Batutu, Roxane, Beaumont, Katy, Béchet, Sibylle, Berchem, Guy, Bisdorff, Alexandre, Boussaad, Ibrahim, Bouvier, David, Castillo, Lorieza, Contesotto, Gessica, De Bremaeker, Nancy, Dewitt, Brian, Diederich, Nico, Dondelinger, Rene, Ramia, Nancy E, Ferrari, Angelo, Frauenknecht, Katrin, Fritz, Joëlle, Gamio, Carlos, Gantenbein, Manon, Gawron, Piotr, Georges, Laura, Ghosh, Soumyabrata, Giraitis, Marijus, Glaab, Enrico, Goergen, Martine, Gómez De Lope, Elisa, Graas, Jérôme, Graziano, Mariella, Groues, Valentin, Grünewald, Anne, Hammot, Gaël, Hanff, Anne-Marie, Hansen, Linda, Heneka, Michael, Henry, Estelle, Henry, Margaux, Herbrink, Sylvia, Herzinger, Sascha, Hundt, Alexander, Jacoby, Nadine, Jónsdóttir, Sonja, Klucken, Jochen, Kofanova, Olga, Krüger, Rejko, Lambert, Pauline, Landoulsi, Zied, Lentz, Roseline, Longhino, Laura, Lopes, Ana Festas, Lorentz, Victoria, Marques, Tainá M., Marques, Guilherme, Martins Conde, Patricia, May, Patrick, Mcintyre, Deborah, Mediouni, Chouaib, Meisch, Francoise, Mendibide, Alexia, Menster, Myriam, Minelli, Maura, Mittelbronn, Michel, Mtimet, Saïda, Munsch, Maeva, Nati, Romain, Nehrbass, Ulf, Nickels, Sarah, Nicolai, Beatrice, Nicolay, Jean-Paul, Noor, Fozia, Gomes, Clarissa P. C., Pachchek, Sinthuja, Pauly, Claire, Pauly, Laure, Pavelka, Lukas, Perquin, Magali, Pexaras, Achilleas, Rauschenberger, Armin, Rawal, Rajesh, Reddy Bobbili, Dheeraj, Remark, Lucie, Richard, Ilsé, Roland, Olivia, Roomp, Kirsten, Rosales, Eduardo, Sapienza, Stefano, Satagopam, Venkata, Schmitz, Sabine, Schneider, Reinhard, Schwamborn, Jens, Severino, Raquel, Sharify, Amir, Soare, Ruxandra, Soboleva, Ekaterina, Sokolowska, Kate, Theresine, Maud, Thien, Hermann, Thiry, Elodie, Ting Jiin Loo, Rebecca, Trouet, Johanna, Tsurkalenko, Olena, Vaillant, Michel, Vega, Carlos, Vilas Boas, Liliana, Wilmes, Paul, Wollscheid-Lengeling, Evi, and Zelimkhanov, Gelani

Published
2024
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2. Levodopa-induced dyskinesia in Parkinson's disease: Insights from cross-cohort prognostic analysis using machine learning

Author

Acharya, Geeta, Aguayo, Gloria, Alexandre, Myriam, Ali, Muhammad, Ammerlann, Wim, Arena, Giuseppe, Bassis, Michele, Batutu, Roxane, Beaumont, Katy, Béchet, Sibylle, Berchem, Guy, Bisdorff, Alexandre, Boussaad, Ibrahim, Bouvier, David, Castillo, Lorieza, Contesotto, Gessica, DE Bremaeker, Nancy, Dewitt, Brian, Diederich, Nico, Dondelinger, Rene, Ramia, Nancy E., Ferrari, Angelo, Frauenknecht, Katrin, Fritz, Joëlle, Gamio, Carlos, Gantenbein, Manon, Gawron, Piotr, Georges, Laura, Ghosh, Soumyabrata, Giraitis, Marijus, Glaab, Enrico, Goergen, Martine, Gómez DE Lope, Elisa, Graas, Jérôme, Graziano, Mariella, Groues, Valentin, Grünewald, Anne, Hammot, Gaël, Anne-Marie, H.A.N.F.F., Hansen, Linda, Heneka, Michael, Henry, Estelle, Henry, Margaux, Herbrink, Sylvia, Herzinger, Sascha, Hundt, Alexander, Jacoby, Nadine, Jónsdóttir, Sonja, Klucken, Jochen, Kofanova, Olga, Krüger, Rejko, Lambert, Pauline, Landoulsi, Zied, Lentz, Roseline, Longhino, Laura, Lopes, Ana Festas, Lorentz, Victoria, Marques, Tainá M., Marques, Guilherme, Martins Conde, Patricia, Patrick, M.A.Y., Mcintyre, Deborah, Mediouni, Chouaib, Meisch, Francoise, Mendibide, Alexia, Menster, Myriam, Minelli, Maura, Mittelbronn, Michel, Mtimet, Saïda, Munsch, Maeva, Nati, Romain, Nehrbass, Ulf, Nickels, Sarah, Nicolai, Beatrice, Jean-Paul, N.I.C.O.L.A.Y., Noor, Fozia, Gomes, Clarissa P.C., Pachchek, Sinthuja, Pauly, Claire, Pauly, Laure, Pavelka, Lukas, Perquin, Magali, Pexaras, Achilleas, Rauschenberger, Armin, Rawal, Rajesh, Reddy Bobbili, Dheeraj, Remark, Lucie, Richard, Ilsé, Roland, Olivia, Roomp, Kirsten, Rosales, Eduardo, Sapienza, Stefano, Satagopam, Venkata, Schmitz, Sabine, Schneider, Reinhard, Schwamborn, Jens, Severino, Raquel, Sharify, Amir, Soare, Ruxandra, Soboleva, Ekaterina, Sokolowska, Kate, Theresine, Maud, Thien, Hermann, Thiry, Elodie, Ting Jiin Loo, Rebecca, Trouet, Johanna, Tsurkalenko, Olena, Vaillant, Michel, Vega, Carlos, Vilas Boas, Liliana, Wilmes, Paul, Wollscheid-Lengeling, Evi, Zelimkhanov, Gelani, Loo, Rebecca Ting Jiin, Mangone, Graziella, Khoury, Fouad, Vidailhet, Marie, and Corvol, Jean-Christophe

Published
2024
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3. Parkinson’s disease-associated alterations of the gut microbiome predict disease-relevant changes in metabolic functions

Author

Baldini, Federico, Hertel, Johannes, Sandt, Estelle, Thinnes, Cyrille C., Neuberger-Castillo, Lorieza, Pavelka, Lukas, Betsou, Fay, Krüger, Rejko, Thiele, Ines, Aguayo, Gloria, Allen, Dominic, Ammerlann, Wim, Aurich, Maike, Balling, Rudi, Banda, Peter, Beaumont, Katy, Becker, Regina, Berg, Daniela, Binck, Sylvia, Bisdorff, Alexandre, Bobbili, Dheeraj, Brockmann, Kathrin, Calmes, Jessica, Castillo, Lorieza, Diederich, Nico, Dondelinger, Rene, Esteves, Daniela, Ferrand, Jean-Yves, Fleming, Ronan, Gantenbein, Manon, Gasser, Thomas, Gawron, Piotr, Geffers, Lars, Giarmana, Virginie, Glaab, Enrico, Gomes, Clarissa P. C., Goncharenko, Nikolai, Graas, Jérôme, Graziano, Mariela, Groues, Valentin, Grünewald, Anne, Gu, Wei, Hammot, Gaël, Hanff, Anne-Marie, Hansen, Linda, Hansen, Maxime, Haraldsdöttir, Hulda, Heirendt, Laurent, Herbrink, Sylvia, Herzinger, Sascha, Heymann, Michael, Hiller, Karsten, Hipp, Geraldine, Hu, Michele, Huiart, Laetitia, Hundt, Alexander, Jacoby, Nadine, Jarosław, Jacek, Jaroz, Yohan, Kolber, Pierre, Kutzera, Joachim, Landoulsi, Zied, Larue, Catherine, Lentz, Roseline, Liepelt, Inga, Liszka, Robert, Longhino, Laura, Lorentz, Victoria, Mackay, Clare, Maetzler, Walter, Marcus, Katrin, Marques, Guilherme, Martens, Jan, Mathay, Conny, Matyjaszczyk, Piotr, May, Patrick, Meisch, Francoise, Menster, Myriam, Minelli, Maura, Mittelbronn, Michel, Mollenhauer, Brit, Mommaerts, Kathleen, Moreno, Carlos, Mühlschlegel, Friedrich, Nati, Romain, Nehrbass, Ulf, Nickels, Sarah, Nicolai, Beatrice, Nicolay, Jean-Paul, Noronha, Alberto, Oertel, Wolfgang, Ostaszewski, Marek, Pachchek, Sinthuja, Pauly, Claire, Perquin, Magali, Reiter, Dorothea, Rosety, Isabel, Rump, Kirsten, Satagopam, Venkata, Schlesser, Marc, Schmitz, Sabine, Schmitz, Susanne, Schneider, Reinhard, Schwamborn, Jens, Schweicher, Alexandra, Simons, Janine, Stute, Lara, Trefois, Christophe, Trezzi, Jean-Pierre, Vaillant, Michel, Vasco, Daniel, Vyas, Maharshi, Wade-Martins, Richard, and Wilmes, Paul

Subjects
Male, Systemic disease, Parkinson's disease, Physiology, Luxembourg, Plant Science, Disease, Transsulfuration pathway, Biology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Structural Biology, RNA, Ribosomal, 16S, Pantothenic acid, medicine, Humans, Microbiome, lcsh:QH301-705.5, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, Aged, Metabolic modelling, 0303 health sciences, Gut microbiome, Methionine, Dopaminergic, Parkinson Disease, Cell Biology, Middle Aged, medicine.disease, 3. Good health, Gastrointestinal Microbiome, RNA, Bacterial, chemistry, Computational modelling, lcsh:Biology (General), Case-Control Studies, Parkinson’s disease, Female, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, Developmental Biology, Biotechnology, Research Article
Abstract

Background Parkinson’s disease (PD) is a systemic disease clinically defined by the degeneration of dopaminergic neurons in the brain. While alterations in the gut microbiome composition have been reported in PD, their functional consequences remain unclear. Herein, we addressed this question by an analysis of stool samples from the Luxembourg Parkinson’s Study (n = 147 typical PD cases, n = 162 controls). Results All individuals underwent detailed clinical assessment, including neurological examinations and neuropsychological tests followed by self-reporting questionnaires. Stool samples from these individuals were first analysed by 16S rRNA gene sequencing. Second, we predicted the potential secretion for 129 microbial metabolites through personalised metabolic modelling using the microbiome data and genome-scale metabolic reconstructions of human gut microbes. Our key results include the following. Eight genera and seven species changed significantly in their relative abundances between PD patients and healthy controls. PD-associated microbial patterns statistically depended on sex, age, BMI, and constipation. Particularly, the relative abundances of Bilophila and Paraprevotella were significantly associated with the Hoehn and Yahr staging after controlling for the disease duration. Furthermore, personalised metabolic modelling of the gut microbiomes revealed PD-associated metabolic patterns in the predicted secretion potential of nine microbial metabolites in PD, including increased methionine and cysteinylglycine. The predicted microbial pantothenic acid production potential was linked to the presence of specific non-motor symptoms. Conclusion Our results suggest that PD-associated alterations of the gut microbiome can translate into substantial functional differences affecting host metabolism and disease phenotype.

Published
2020
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4. The Luxembourg Parkinson’s Study: A Comprehensive Approach for Stratification and Early Diagnosis

Author

Hipp, Geraldine, primary, Vaillant, Michel, additional, Diederich, Nico J., additional, Roomp, Kirsten, additional, Satagopam, Venkata P., additional, Banda, Peter, additional, Sandt, Estelle, additional, Mommaerts, Kathleen, additional, Schmitz, Sabine K., additional, Longhino, Laura, additional, Schweicher, Alexandra, additional, Hanff, Anne-Marie, additional, Nicolai, Béatrice, additional, Kolber, Pierre, additional, Reiter, Dorothea, additional, Pavelka, Lukas, additional, Binck, Sylvia, additional, Pauly, Claire, additional, Geffers, Lars, additional, Betsou, Fay, additional, Gantenbein, Manon, additional, Klucken, Jochen, additional, Gasser, Thomas, additional, Hu, Michele T., additional, Balling, Rudi, additional, and Krüger, Rejko, additional

Published
2018
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5. The Luxembourg Parkinson’s Study: A Comprehensive Approach for Stratification and Early Diagnosis

Author

Luxembourg Centre for Systems Biomedicine (LCSB) [research center], Hipp Epouse D'amico, Géraldine, Vaillant, Michel, Diederich, Nico J., Roomp, Kirsten, Satagopam, Venkata, Banda, Peter, Sandt, Estelle, Mommaerts, Kathleen, Schmitz, Sabine, Longhino, Laura, Schweicher, Alexandra, Hanff, Anne-Marie, Nicolai, Béatrice, Kolber, Pierre Luc, Reiter, Dorothea, Pavelka, Lukas, Binck, Sylvia, Pauly, Claire, Geffers, Lars, Betsou, Fay, Gantenbein, Manon, Klucken, Jochen, Gasser, Thomas, Hu, Michele, Balling, Rudi, Krüger, Rejko, Luxembourg Centre for Systems Biomedicine (LCSB) [research center], Hipp Epouse D'amico, Géraldine, Vaillant, Michel, Diederich, Nico J., Roomp, Kirsten, Satagopam, Venkata, Banda, Peter, Sandt, Estelle, Mommaerts, Kathleen, Schmitz, Sabine, Longhino, Laura, Schweicher, Alexandra, Hanff, Anne-Marie, Nicolai, Béatrice, Kolber, Pierre Luc, Reiter, Dorothea, Pavelka, Lukas, Binck, Sylvia, Pauly, Claire, Geffers, Lars, Betsou, Fay, Gantenbein, Manon, Klucken, Jochen, Gasser, Thomas, Hu, Michele, Balling, Rudi, and Krüger, Rejko

Abstract

While genetic advances have successfully defined part of the complexity in Parkinson’s disease (PD), the clinical characterization of phenotypes remains challenging. Therapeutic trials and cohort studies typically include patients with earlier disease stages and exclude comorbidities, thus ignoring a substantial part of the real-world PD population. To account for these limitations, we implemented the Luxembourg PD study as a comprehensive clinical, molecular and device-based approach including patients with typical PD and atypical parkinsonism, irrespective of their disease stage, age, comorbidities, or linguistic background. To provide a large, longitudinally followed, and deeply phenotyped set of patients and controls for clinical and fundamental research on PD, we implemented an open-source digital platform that can be harmonized with international PD cohort studies. Our interests also reflect Luxembourg-specific areas of PD research, including vision, gait, and cognition. This effort is flanked by comprehensive biosampling efforts assuring high quality and sustained availability of body liquids and tissue biopsies. We provide evidence for the feasibility of such a cohort program with deep phenotyping and high quality biosampling on parkinsonism in an environment with structural specificities and alert the international research community to our willingness to collaborate with other centers. The combination of advanced clinical phenotyping approaches including device-based assessment will create a comprehensive assessment of the disease and its variants, its interaction with comorbidities and its progression. We envision the Luxembourg Parkinson’s study as an important research platform for defining early diagnosis and progression markers that translate into stratified treatment approaches.

Published
2018

8. Platelet mitochondrial membrane potential in Parkinson's disease.

Author

Antony, Paul, Boyd, Olga, Trefois, Christophe, Ammerlaan, Wim, Ostaszewski, Marek, Baumuratov, Aidos S., Longhino, Laura, Antunes, Laurent, Koopman, Werner, Balling, Rudi, Diederich, Nico J., Antony, Paul, Boyd, Olga, Trefois, Christophe, Ammerlaan, Wim, Ostaszewski, Marek, Baumuratov, Aidos S., Longhino, Laura, Antunes, Laurent, Koopman, Werner, Balling, Rudi, and Diederich, Nico J.

Abstract

OBJECTIVE: Mitochondrial dysfunction is a hallmark of idiopathic Parkinson's disease (IPD), which has been reported not to be restricted to striatal neurons. However, studies that analyzed mitochondrial function at the level of selected enzymatic activities in peripheral tissues have produced conflicting data. We considered the electron transport chain as a complex system with mitochondrial membrane potential as an integrative indicator for mitochondrial fitness. METHODS: Twenty-five IPD patients (nine females; mean disease duration, 6.2 years) and 16 healthy age-matched controls (12 females) were recruited. Live platelets were purified using magnetic-activated cell sorting (MACS) and single-cell data on mitochondrial membrane potential (Deltapsi) were measured by cytometry and challenged with a protonophore agent. RESULTS: Functional mitochondrial membrane potential was detected in all participants. The challenge test reduced the membrane potential in all IPD patients and controls (P < 0.001). However, the response to the challenge was not significantly different between patients and controls. INTERPRETATION: While the reported protonophore challenge assay is a valid marker of overall mitochondrial function in live platelets, intact mitochondrial membrane potential in platelets derived from IPD patients suggests that presumed mitochondrial enzymatic deficiencies are compensable in this cell type. In consequence, mitochondrial membrane potential in platelets cannot be used as a diagnostic biomarker for nonstratified IPD but should be further explored in potential Parkinson's disease subtypes and tissues with higher energy demands.

Published
2015

9. Platelet mitochondrial membrane potential in Parkinson's disease

Author

Antony, Paul M. A., primary, Boyd, Olga, additional, Trefois, Christophe, additional, Ammerlaan, Wim, additional, Ostaszewski, Marek, additional, Baumuratov, Aidos S., additional, Longhino, Laura, additional, Antunes, Laurent, additional, Koopman, Werner, additional, Balling, Rudi, additional, and Diederich, Nico J., additional

Published
2014
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10. Platelet mitochondrial membrane potential in Parkinson's disease.

Author

Antony, Paul M. A., Boyd, Olga, Trefois, Christophe, Ammerlaan, Wim, Ostaszewski, Marek, Baumuratov, Aidos S., Longhino, Laura, Antunes, Laurent, Koopman, Werner, Balling, Rudi, and Diederich, Nico J.

Subjects
PARKINSON'S disease diagnosis, MITOCHONDRIAL membranes, NEURONS, BIOMARKERS, CYTOMETRY
Abstract

Objective Mitochondrial dysfunction is a hallmark of idiopathic Parkinson's disease ( IPD), which has been reported not to be restricted to striatal neurons. However, studies that analyzed mitochondrial function at the level of selected enzymatic activities in peripheral tissues have produced conflicting data. We considered the electron transport chain as a complex system with mitochondrial membrane potential as an integrative indicator for mitochondrial fitness. Methods Twenty-five IPD patients (nine females; mean disease duration, 6.2 years) and 16 healthy age-matched controls (12 females) were recruited. Live platelets were purified using magnetic-activated cell sorting ( MACS) and single-cell data on mitochondrial membrane potential (∆ ψ) were measured by cytometry and challenged with a protonophore agent. Results Functional mitochondrial membrane potential was detected in all participants. The challenge test reduced the membrane potential in all IPD patients and controls ( P < 0.001). However, the response to the challenge was not significantly different between patients and controls. Interpretation While the reported protonophore challenge assay is a valid marker of overall mitochondrial function in live platelets, intact mitochondrial membrane potential in platelets derived from IPD patients suggests that presumed mitochondrial enzymatic deficiencies are compensable in this cell type. In consequence, mitochondrial membrane potential in platelets cannot be used as a diagnostic biomarker for nonstratified IPD but should be further explored in potential Parkinson's disease subtypes and tissues with higher energy demands. [ABSTRACT FROM AUTHOR]

Published
2015
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