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1. Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson's disease patients

Author

Zago E., Dal Molin A., Dimitri G. M., Xumerle L., Pirazzini C., Bacalini M. G., Maturo M. G., Azevedo T., Spasov S., Gomez-Garre P., Perinan M. T., Jesus S., Baldelli L., Sambati L., Calandra Buonaura G., Garagnani P., Provini F., Cortelli P., Mir P., Trenkwalder C., Mollenhauer B., Franceschi C., Lio P., Nardini C., Adarmes-Gomez A., Bartoletti-Stella A., Bhatia K. P., Marta B. -T., Boninsegna C., Broli M., Dolores B. -R., Calandra-Buonaura G., Capellari S., Carrion-Claro M., Cilea R., Clayton R., Molin A. D., De Luca S., De Massis P., Doykov I., Escuela-Martin R., Fabbri G., Gabellini A., Giuliani C., Guaraldi P., Hagg S., Hallqvist J., Halsband C., Heywood W., Houlden H., Huertas I., Jylhava J., Labrador-Espinosa M. A., Licari C., Luchinat C., Macias D., Macri S., Magrinelli F., Rodriguez J. F. M., Massimo D., Mengozzi G., Meoni G., Mignani F., Milazzo M., Mills K., Nassetti S. A., Pedersen N. L., Perinan-Tocino M. T., Ravaioli F., Sala C., Scaglione C. L. M., Schade S., Schreglmann S., Strom S., Tejera-Parrado C., Tenori L., Turano P., Valzania F., Ortega R. V., Williams D., Apollo - University of Cambridge Repository, Zago E., Dal Molin A., Dimitri G.M., Xumerle L., Pirazzini C., Bacalini M.G., Maturo M.G., Azevedo T., Spasov S., Gomez-Garre P., Perinan M.T., Jesus S., Baldelli L., Sambati L., Calandra Buonaura G., Garagnani P., Provini F., Cortelli P., Mir P., Trenkwalder C., Mollenhauer B., Franceschi C., Lio P., Nardini C., Adarmes-Gomez A., Bartoletti-Stella A., Bhatia K.P., Marta B.-T., Boninsegna C., Broli M., Dolores B.-R., Calandra-Buonaura G., Capellari S., Carrion-Claro M., Cilea R., Clayton R., Molin A.D., De Luca S., De Massis P., Doykov I., Escuela-Martin R., Fabbri G., Gabellini A., Giuliani C., Guaraldi P., Hagg S., Hallqvist J., Halsband C., Heywood W., Houlden H., Huertas I., Jylhava J., Labrador-Espinosa M.A., Licari C., Luchinat C., Macias D., Macri S., Magrinelli F., Rodriguez J.F.M., Massimo D., Mengozzi G., Meoni G., Mignani F., Milazzo M., Mills K., Nassetti S.A., Pedersen N.L., Perinan-Tocino M.T., Ravaioli F., Sala C., Scaglione C.L.M., Schade S., Schreglmann S., Strom S., Tejera-Parrado C., Tenori L., Turano P., Valzania F., Ortega R.V., and Williams D.

Subjects
Male, Aging, Molecular biology, Science, Immunology, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Medical research, Humans, Parkinson, 030304 developmental biology, Aged, 0303 health sciences, Multidisciplinary, Biological techniques, Parkinson Disease, Middle Aged, 3. Good health, nervous system diseases, Computational biology and bioinformatics, MicroRNAs, Neurology, ageing, Medicine, Female, 030217 neurology & neurosurgery, Biomarkers
Abstract

Advanced age represents one of the major risk factors for Parkinson's Disease. Recent biomedical studies posit a role for microRNAs, also known to be remodelled during ageing. However, the relationship between microRNA remodelling and ageing in Parkinson's Disease, has not been fully elucidated. Therefore, the aim of the present study is to unravel the relevance of microRNAs as biomarkers of Parkinson's Disease within the ageing framework. We employed Next Generation Sequencing to profile serum microRNAs from samples informative for Parkinson's Disease (recently diagnosed, drug-naïve) and healthy ageing (centenarians) plus healthy controls, age-matched with Parkinson's Disease patients. Potential microRNA candidates markers, emerging from the combination of differential expression and network analyses, were further validated in an independent cohort including both drug-naïve and advanced Parkinson's Disease patients, and healthy siblings of Parkinson's Disease patients at higher genetic risk for developing the disease. While we did not find evidences of microRNAs co-regulated in Parkinson's Disease and ageing, we report that hsa-miR-144-3p is consistently down-regulated in early Parkinson's Disease patients. Moreover, interestingly, functional analysis revealed that hsa-miR-144-3p is involved in the regulation of coagulation, a process known to be altered in Parkinson's Disease. Our results consistently show the down-regulation of hsa-mir144-3p in early Parkinson's Disease, robustly confirmed across a variety of analytical and experimental analyses. These promising results ask for further research to unveil the functional details of the involvement of hsa-mir144-3p in Parkinson's Disease., This work was supported by the Horizon 2020 Framework Programme (Grant number 634821, PROPAG-AGING).

Published
2022

2. Self-rated health in individuals with and without disease is associated with multiple biomarkers representing multiple biological domains

Author

Kananen, L., Enroth, L., Raitanen, J., Jylhava, J., Burkle, A., Moreno-Villanueva, M., Bernhardt, J., Toussaint, O., Grubeck-Loebenstein, B., Malavolta, M., Basso, A., Piacenza, F., Collino, S., Gonos, E.S., Sikora, E., Gradinaru, D., Jansen, E.H.J.M., Dolle, M.E.T., Salmon, M., Stuetz, W., Weber, D., Grune, T., Breusing, N., Simm, A., Capri, M., Franceschi, C., Slagboom, P.E., Talbot, D.C.S., Libert, C., Koskinen, S., Bruunsgaard, H., Hansen, A.M., Lund, R., Hurme, M., Jylha, M., Kananen L., Enroth L., Raitanen J., Jylhava J., Burkle A., Moreno-Villanueva M., Bernhardt J., Toussaint O., Grubeck-Loebenstein B., Malavolta M., Basso A., Piacenza F., Collino S., Gonos E.S., Sikora E., Gradinaru D., Jansen E.H.J.M., Dolle M.E.T., Salmon M., Stuetz W., Weber D., Grune T., Breusing N., Simm A., Capri M., Franceschi C., Slagboom P.E., Talbot D.C.S., Libert C., Koskinen S., Bruunsgaard H., Hansen A., Lund R., Hurme M., Jylha M., Tampere University, Health Sciences, and BioMediTech

Subjects
Quality of life, Adult, Male, Aging, Adolescent, Health Status, Science, education, Predictive markers, Article, Diagnostic Self Evaluation, Young Adult, ddc:570, Medicine and Health Sciences, Humans, Aged, Aged, 80 and over, Health care, Biology and Life Sciences, biomarkers, Middle Aged, 3141 Health care science, body regions, Somatosensory system, Medicine, Female, 3111 Biomedicine, Self Report
Abstract

Self-rated health (SRH) is one of the most frequently used indicators in health and social research. Its robust association with mortality in very different populations implies that it is a comprehensive measure of health status and may even reflect the condition of the human organism beyond clinical diagnoses. Yet the biological basis of SRH is poorly understood. We used data from three independent European population samples (N approx. 15,000) to investigate the associations of SRH with 150 biomolecules in blood or urine (biomarkers). Altogether 57 biomarkers representing different organ systems were associated with SRH. In almost half of the cases the association was independent of disease and physical functioning. Biomarkers weakened but did not remove the association between SRH and mortality. We propose three potential pathways through which biomarkers may be incorporated into an individual’s subjective health assessment, including (1) their role in clinical diseases; (2) their association with health-related lifestyles; and (3) their potential to stimulate physical sensations through interoceptive mechanisms. Our findings indicate that SRH has a solid biological basis and it is a valid but non-specific indicator of the biological condition of the human organism. publishedVersion

Published
2021
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3. Early downregulation of hsa-miR-144-3p in serum from drug-naïve Parkinson’s disease patients

Author

Zago, E., Dal Molin, A., Dimitri, G. M., Xumerle, L., Pirazzini, C., Bacalini, M. G., Maturo, M. G., Azevedo, T., Spasov, S., Gomez-Garre, P., Perinan, M. T., Jesus, S., Baldelli, L., Sambati, L., Calandra-Buonaura, G., Garagnani, P., Provini, F., Cortelli, P., Mir, P., Trenkwalder, C., Mollenhauer, B., Franceschi, C., Lio, P., Nardini, C., Adarmes-Gomez, A., Bartoletti-Stella, A., Bhatia, K. P., Marta, B. -T., Boninsegna, C., Broli, M., Dolores, B. -R., Capellari, S., Carrion-Claro, M., Cilea, R., Clayton, R., Molin, A. D., De Luca, S., De Massis, P., Doykov, I., Escuela-Martin, R., Fabbri, G., Gabellini, A., Giuliani, C., Guaraldi, P., Hagg, S., Hallqvist, J., Halsband, C., Heywood, W., Houlden, H., Huertas, I., Jylhava, J., Labrador-Espinosa, M. A., Licari, C., Luchinat, C., Macias, D., Macri, S., Magrinelli, F., Rodriguez, J. F. M., Massimo, D., Mengozzi, G., Meoni, G., Mignani, F., Milazzo, M., Mills, K., Nassetti, S. A., Pedersen, N. L., Perinan-Tocino, M. T., Ravaioli, F., Sala, C., Scaglione, C. L. M., Schade, S., Schreglmann, S., Strom, S., Tejera-Parrado, C., Tenori, L., Turano, P., Valzania, F., Ortega, R. V., and Williams, D.

Subjects
hsa‑miR‑144‑3p, serum, Parkinson’s disease patients
Published
2022

4. DNA methylation signatures of aggression and closely related constructs:a meta-analysis of epigenome-wide studies across the lifespan

Author

van Dongen, J. (Jenny), Hagenbeek, F. A. (Fiona A.), Suderman, M. (Matthew), Roetman, P. J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A. G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R. H. (Rosa H.), Hafferty, J. D. (Jonathan D.), Adams, M. J. (Mark J.), Walker, R. M. (Rosie M.), Morris, S. W. (Stewart W.), Lahti, J. (Jari), Kupers, L. K. (Leanne K.), Escaramis, G. (Georgia), Alemany, S. (Silvia), Bonder, M. J. (Marc Jan), Meijer, M. (Mandy), Ip, H. F. (Hill F.), Jansen, R. (Rick), Baselmans, B. M. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T. S. (Tabea S.), Frank, J. (Josef), Jylhava, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P. P. (Pashupati Prasad), Colins, O. F. (Olivier F.), Corcoran, D. L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J. F. (Janine F.), Bakermans-Kranenburg, M. J. (Marian J.), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J. R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K. B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G. E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Jarvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C. M. (Christine M.), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernandez-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimaki, T. (Terho), Vermeiren, R. (Robert), Strandberg, T. (Timo), Raikkonen, K. (Katri), Snieder, H. (Harold), Witt, S. H. (Stephanie H.), Deuschle, M. (Michael), Pedersen, N. L. (Nancy L.), Hagg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T. E. (Terrie E.), Tiemeier, H. (Henning), van IJzendoorn, M. H. (Marinus H.), Relton, C. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Järvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K. L. (Kathryn L.), McIntosh, A. M. (Andrew M.), Bartels, M. (Meike), Boomsma, D. I. (Dorret, I), van Dongen, J. (Jenny), Hagenbeek, F. A. (Fiona A.), Suderman, M. (Matthew), Roetman, P. J. (Peter J.), Sugden, K. (Karen), Chiocchetti, A. G. (Andreas G.), Ismail, K. (Khadeeja), Mulder, R. H. (Rosa H.), Hafferty, J. D. (Jonathan D.), Adams, M. J. (Mark J.), Walker, R. M. (Rosie M.), Morris, S. W. (Stewart W.), Lahti, J. (Jari), Kupers, L. K. (Leanne K.), Escaramis, G. (Georgia), Alemany, S. (Silvia), Bonder, M. J. (Marc Jan), Meijer, M. (Mandy), Ip, H. F. (Hill F.), Jansen, R. (Rick), Baselmans, B. M. (Bart M. L.), Parmar, P. (Priyanka), Lowry, E. (Estelle), Streit, F. (Fabian), Sirignano, L. (Lea), Send, T. S. (Tabea S.), Frank, J. (Josef), Jylhava, J. (Juulia), Wang, Y. (Yunzhang), Mishra, P. P. (Pashupati Prasad), Colins, O. F. (Olivier F.), Corcoran, D. L. (David L.), Poulton, R. (Richie), Mill, J. (Jonathan), Hannon, E. (Eilis), Arseneault, L. (Louise), Korhonen, T. (Tellervo), Vuoksimaa, E. (Eero), Felix, J. F. (Janine F.), Bakermans-Kranenburg, M. J. (Marian J.), Campbell, A. (Archie), Czamara, D. (Darina), Binder, E. (Elisabeth), Corpeleijn, E. (Eva), Gonzalez, J. R. (Juan R.), Grazuleviciene, R. (Regina), Gutzkow, K. B. (Kristine B.), Evandt, J. (Jorunn), Vafeiadi, M. (Marina), Klein, M. (Marieke), van der Meer, D. (Dennis), Ligthart, L. (Lannie), Kluft, C. (Cornelis), Davies, G. E. (Gareth E.), Hakulinen, C. (Christian), Keltikangas-Jarvinen, L. (Liisa), Franke, B. (Barbara), Freitag, C. M. (Christine M.), Konrad, K. (Kerstin), Hervas, A. (Amaia), Fernandez-Rivas, A. (Aranzazu), Vetro, A. (Agnes), Raitakari, O. (Olli), Lehtimaki, T. (Terho), Vermeiren, R. (Robert), Strandberg, T. (Timo), Raikkonen, K. (Katri), Snieder, H. (Harold), Witt, S. H. (Stephanie H.), Deuschle, M. (Michael), Pedersen, N. L. (Nancy L.), Hagg, S. (Sara), Sunyer, J. (Jordi), Franke, L. (Lude), Kaprio, J. (Jaakko), Ollikainen, M. (Miina), Moffitt, T. E. (Terrie E.), Tiemeier, H. (Henning), van IJzendoorn, M. H. (Marinus H.), Relton, C. (Caroline), Vrijheid, M. (Martine), Sebert, S. (Sylvain), Järvelin, M.-R. (Marjo-Riitta), Caspi, A. (Avshalom), Evans, K. L. (Kathryn L.), McIntosh, A. M. (Andrew M.), Bartels, M. (Meike), and Boomsma, D. I. (Dorret, I)

Abstract

DNA methylation profiles of aggressive behavior may capture lifetime cumulative effects of genetic, stochastic, and environmental influences associated with aggression. Here, we report the first large meta-analysis of epigenome-wide association studies (EWAS) of aggressive behavior (N = 15,324 participants). In peripheral blood samples of 14,434 participants from 18 cohorts with mean ages ranging from 7 to 68 years, 13 methylation sites were significantly associated with aggression (alpha = 1.2 × 10−7; Bonferroni correction). In cord blood samples of 2425 children from five cohorts with aggression assessed at mean ages ranging from 4 to 7 years, 83% of these sites showed the same direction of association with childhood aggression (r = 0.74, p = 0.006) but no epigenome-wide significant sites were found. Top-sites (48 at a false discovery rate of 5% in the peripheral blood meta-analysis or in a combined meta-analysis of peripheral blood and cord blood) have been associated with chemical exposures, smoking, cognition, metabolic traits, and genetic variation (mQTLs). Three genes whose expression levels were associated with top-sites were previously linked to schizophrenia and general risk tolerance. At six CpGs, DNA methylation variation in blood mirrors variation in the brain. On average 44% (range = 3–82%) of the aggression–methylation association was explained by current and former smoking and BMI. These findings point at loci that are sensitive to chemical exposures with potential implications for neuronal functions. We hope these results to be a starting point for studies leading to applications as peripheral biomarkers and to reveal causal relationships with aggression and related traits.

Published
2021

5. Circulating cell-free DNA in health and disease - the relationship to health behaviours, ageing phenotypes and metabolomics

Author

Laura Kananen, Mikko Hurme, Alexander Bürkle, Maria Moreno-Villanueva, Jürgen Bernhardt, Florence Debacq-Chainiaux, Beatrix Grubeck-Loebenstein, Marco Malavolta, Andrea Basso, Francesco Piacenza, Sebastiano Collino, Efstathios S. Gonos, Ewa Sikora, Daniela Gradinaru, Eugene H. J. M. Jansen, Martijn E. T. Dollé, Michel Salmon, Wolfgang Stuetz, Daniela Weber, Tilman Grune, Nicolle Breusing, Andreas Simm, Miriam Capri, Claudio Franceschi, Eline Slagboom, Duncan Talbot, Claude Libert, Jani Raitanen, Seppo Koskinen, Tommi Härkänen, Sari Stenholm, Mika Ala-Korpela, Terho Lehtimäki, Olli T. Raitakari, Olavi Ukkola, Mika Kähönen, Marja Jylhä, Juulia Jylhävä, Tampere University, Health Sciences, BioMediTech, Department of Clinical Chemistry, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, Kananen L., Hurme M., Burkle A., Moreno-Villanueva M., Bernhardt J., Debacq-Chainiaux F., Grubeck-Loebenstein B., Malavolta M., Basso A., Piacenza F., Collino S., Gonos E.S., Sikora E., Gradinaru D., Jansen E.H.J.M., Dolle M.E.T., Salmon M., Stuetz W., Weber D., Grune T., Breusing N., Simm A., Capri M., Franceschi C., Slagboom E., Talbot D., Libert C., Raitanen J., Koskinen S., Harkanen T., Stenholm S., Ala-Korpela M., Lehtimaki T., Raitakari O.T., Ukkola O., Kahonen M., Jylha M., and Jylhava J.

Subjects
Aging, Frailty, Biology and Life Sciences, Metabolomic, 3121 Internal medicine, 3142 Public health care science, environmental and occupational health, 3141 Health care science, Cell-free DNA, Health behaviours, Medicine and Health Sciences, Health behaviour, Metabolomics, 3111 Biomedicine, Geriatrics and Gerontology, Morbidity, Biomarker of ageing
Abstract

Circulating cell-free DNA (cf-DNA) has emerged as a promising biomarker of ageing, tissue damage and cellular stress. However, less is known about health behaviours, ageing phenotypes and metabolic processes that lead to elevated cf-DNA levels. We sought to analyse the relationship of circulating cf-DNA level to age, sex, smoking, physical activity, vegetable consumption, ageing phenotypes (physical functioning, the number of diseases, frailty) and an extensive panel of biomarkers including blood and urine metabolites and inflammatory markers in three human cohorts (N = 5385; 17–82 years). The relationships were assessed using correlation statistics, and linear and penalised regressions (the Lasso), also stratified by sex.cf-DNA levels were significantly higher in men than in women, and especially in middle-aged men and women who smoke, and in older more frail individuals. Correlation statistics of biomarker data showed that cf-DNA level was higher with elevated inflammation (C-reactive protein, interleukin-6), and higher levels of homocysteine, and proportion of red blood cells and lower levels of ascorbic acid. Inflammation (C-reactive protein, glycoprotein acetylation), amino acids (isoleucine, leucine, tyrosine), and ketogenesis (3-hydroxybutyrate) were included in the cf-DNA level-related biomarker profiles in at least two of the cohorts.In conclusion, circulating cf-DNA level is different by sex, and related to health behaviour, health decline and metabolic processes common in health and disease. These results can inform future studies where epidemiological and biological pathways of cf-DNA are to be analysed in details, and for studies evaluating cf-DNA as a potential clinical marker.

Published
2023
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6. Heterogeneity of prodromal Parkinson symptoms in siblings of Parkinson disease patients

Author

Baldelli, Luca, Schade, Sebastian, Jesús, Silvia, Schreglmann, Sebastian R., Sambati, Luisa, Gómez-Garre, Pilar, Halsband, Claire, Calandra-Buonaura, Giovanna, Adarmes-Gómez, Astrid Daniela, Sixel-Döring, Friederike, Zenesini, Corrado, Pirazzini, Chiara, Garagnani, Paolo, Bacalini, Maria Giulia, Bhatia, Kailash P., Cortelli, Pietro, Mollenhauer, Brit, Franceschi, Claudio, Houlden, Henry, Liò, Pietro, Luchinat, Claudio, Delledonne, Massimo, Mills, Kevin, Pedersen, Nancy L., Azevedo, Tiago, Bartoletti-Stella, Anna, Bonilla-Toribio, Marta, Buiza-Rueda, Dolores, Capellari, Sabina, Carriòn-Claro, Mario, Clayton, Robert, Dal Molin, Alessandra, Dimitri, Giovanna Maria, Doykov, Ivan, Giuliani, Cristina, Hägg, Sara, Hällqvist, Jenny, Heywood, Wendy, Huertas, Ismael, Jylhävä, Juulia, Labrador-Espinosa, Miguel A., Licari, Cristina, Macias, Daniel, Magrinelli, Francesca, Rodríguez, Juan Francisco Martín, Maturo, Maria Giovanna, Mengozzi, Giacomo, Meoni, Gaia, Milazzo, Maddalena, Nardini, Christine, Periñán-Tocino, Maria Teresa, Ravaioli, Francesco, Sala, Claudia, Spasov, Simeon, Tejera-Parrado, Cristina, Tenori, Leonardo, Paola, Turano, Williams, Dylan, Xumerle, Luciano, Zago, Elisa, Broli, Marcella, De Massis, Patrizia, Escuela-Martin, Rocio, Fabbri, Giovanni, Gabellini, Anna, Guaraldi, Pietro, Macrì, Stefania, Nassetti, Stefania Alessandra, Scaglione, Cesa Lorella Maria, Valzania, Franco, Rosaria, Cilea, Mignani, Francesco, Ortega, Rosario Vigo, Boninsegna, Claudia, De Luca, Silvia, Mir, Pablo, Trenkwalder, Claudia, Provini, Federica, European Commission, Schade, Sebastian [0000-0002-6316-6804], Gómez-Garre, Pilar [0000-0002-0437-6182], Mir, Pablo [0000-0003-1656-302X], Provini, Federica [0000-0001-9063-2658], Apollo - University of Cambridge Repository, Baldelli L., Schade S., Jesus S., Schreglmann S.R., Sambati L., Gomez-Garre P., Halsband C., Calandra Buonaura G., Adarmes-Gomez A.D., Sixel-Doring F., Zenesini C., Pirazzini C., Garagnani P., Bacalini M.G., Bhatia K.P., Cortelli P., Mollenhauer B., Franceschi C., Houlden H., Lio P., Luchinat C., Delledonne M., Mills K., Pedersen N.L., Azevedo T., Bartoletti-Stella A., Bonilla-Toribio M., Buiza-Rueda D., Capellari S., Carrion-Claro M., Clayton R., Dal Molin A., Dimitri G.M., Doykov I., Giuliani C., Hagg S., Hallqvist J., Heywood W., Huertas I., Jylhava J., Labrador-Espinosa M.A., Licari C., Macias D., Magrinelli F., Rodriguez J.F.M., Maturo M.G., Mengozzi G., Meoni G., Milazzo M., Nardini C., Perinan-Tocino M.T., Ravaioli F., Sala C., Spasov S., Tejera-Parrado C., Tenori L., Paola T., Williams D., Xumerle L., Zago E., Broli M., De Massis P., Escuela-Martin R., Fabbri G., Gabellini A., Guaraldi P., Macri S., Nassetti S.A., Scaglione C.L.M., Valzania F., Rosaria C., Mignani F., Ortega R.V., Boninsegna C., De Luca S., Mir P., Trenkwalder C., and Provini F.

Subjects
Pediatrics, medicine.medical_specialty, Parkinson's disease, MathematicsofComputing_GENERAL, Disease, prodromal symptom, Predictive markers, REM sleep behavior disorder, Article, 03 medical and health sciences, Cellular and Molecular Neuroscience, Orthostatic vital signs, 0302 clinical medicine, 030225 pediatrics, Medicine, Motor Manifestations, Disease markers, RC346-429, siblings, business.industry, TheoryofComputation_GENERAL, Cognition, Parkinson Disease, medicine.disease, 3. Good health, metabolomics, parkinson disease, Neurology, Risk factors, Cohort, PD, Neurology. Diseases of the nervous system, Neurology (clinical), PROPAG-AGEING consortium, business, 030217 neurology & neurosurgery
Abstract

PROPAG-AGEING consortium., A prodromal phase of Parkinson’s disease (PD) may precede motor manifestations by decades. PD patients’ siblings are at higher risk for PD, but the prevalence and distribution of prodromal symptoms are unknown. The study objectives were (1) to assess motor and non-motor features estimating prodromal PD probability in PD siblings recruited within the European PROPAG-AGEING project; (2) to compare motor and non-motor symptoms to the well-established DeNoPa cohort. 340 PD siblings from three sites (Bologna, Seville, Kassel/Goettingen) underwent clinical and neurological evaluations of PD markers. The German part of the cohort was compared with German de novo PD patients (dnPDs) and healthy controls (CTRs) from DeNoPa. Fifteen (4.4%) siblings presented with subtle signs of motor impairment, with MDS-UPDRS-III scores not clinically different from CTRs. Symptoms of orthostatic hypotension were present in 47 siblings (13.8%), no different to CTRs (p = 0.072). No differences were found for olfaction and overall cognition; German-siblings performed worse than CTRs in visuospatial-executive and language tasks. 3/147 siblings had video-polysomnography-confirmed REM sleep behavior disorder (RBD), none was positive on the RBD Screening Questionnaire. 173/300 siblings had, This project has received funding from the European Union’s Horizon 2020 research and innovation program Propag‐Ageing under grant agreement no. 634821.

Published
2021
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7. A geroscience approach for Parkinson's disease: Conceptual framework and design of PROPAG-AGEING project

Author

Chiara Pirazzini, Tiago Azevedo, Luca Baldelli, Anna Bartoletti-Stella, Giovanna Calandra-Buonaura, Alessandra Dal Molin, Giovanna Maria Dimitri, Ivan Doykov, Pilar Gómez-Garre, Sara Hägg, Jenny Hällqvist, Claire Halsband, Wendy Heywood, Silvia Jesús, Juulia Jylhävä, Katarzyna Malgorzata Kwiatkowska, Miguel A. Labrador-Espinosa, Cristina Licari, Maria Giovanna Maturo, Giacomo Mengozzi, Gaia Meoni, Maddalena Milazzo, Maria Teresa Periñán-Tocino, Francesco Ravaioli, Claudia Sala, Luisa Sambati, Sebastian Schade, Sebastian Schreglmann, Simeon Spasov, Leonardo Tenori, Dylan Williams, Luciano Xumerle, Elisa Zago, Kailash P. Bhatia, Sabina Capellari, Pietro Cortelli, Paolo Garagnani, Henry Houlden, Pietro Liò, Claudio Luchinat, Massimo Delledonne, Kevin Mills, Pablo Mir, Brit Mollenhauer, Christine Nardini, Nancy L. Pedersen, Federica Provini, Stephen Strom, Claudia Trenkwalder, Paola Turano, Maria Giulia Bacalini, Claudio Franceschi, Astrid Adarmes-Gómez, Marta Bonilla-Toribio, Claudia Boninsegna, Marcella Broli, Dolores Buiza-Rueda, Mario Carrión-Claro, Rosalia Cilea, Robert Clayton, Silvia De Luca, Patrizia De Massis, Rocio Escuela-Martin, Giovanni Fabbri, Anna Gabellini, Cristina Giuliani, Pietro Guaraldi, Ismae Huertas, Daniel Macias, Stefania Macrì, Francesca Magrinelli, Juan Francisco Martín Rodríguez, Francesco Mignani, Stefania Alessandra Nassetti, Cesa Lorella Maria Scaglione, Cristina Tejera-Parrado, Franco Valzania, Rosario Vigo Ortega, Pirazzini C., Azevedo T., Baldelli L., Bartoletti-Stella A., Calandra Buonaura G., Dal Molin A., Dimitri G.M., Doykov I., Gomez-Garre P., Hagg S., Hallqvist J., Halsband C., Heywood W., Jesus S., Jylhava J., Kwiatkowska K.M., Labrador-Espinosa M.A., Licari C., Maturo M.G., Mengozzi G., Meoni G., Milazzo M., Perinan-Tocino M.T., Ravaioli F., Sala C., Sambati L., Schade S., Schreglmann S., Spasov S., Tenori L., Williams D., Xumerle L., Zago E., Bhatia K.P., Capellari S., Cortelli P., Garagnani P., Houlden H., Lio P., Luchinat C., Delledonne M., Mills K., Mir P., Mollenhauer B., Nardini C., Pedersen N.L., Provini F., Strom S., Trenkwalder C., Turano P., Bacalini M.G., Franceschi C., Adarmes-Gomez A., Bonilla-Toribio M., Boninsegna C., Broli M., Buiza-Rueda D., Carrion-Claro M., Cilea R., Clayton R., Molin A.D., De Luca S., De Massis P., Escuela-Martin R., Fabbri G., Gabellini A., Giuliani C., Guaraldi P., Huertas I., Macias D., Macri S., Magrinelli F., Rodriguez J.F.M., Mignani F., Nassetti S.A., Scaglione C.L.M., Tejera-Parrado C., Valzania F., and Ortega R.V.

Subjects
0301 basic medicine, Gerontology, Male, Aging, Parkinson's disease, Biomedical Research, Inflammaging, Neurodegeneration, Omics, Disease, Motor Activity, 03 medical and health sciences, 0302 clinical medicine, Omic, medicine, Humans, Metabolomics, Risk factor, Aged, Aged, 80 and over, Neurons, Geroscience, business.industry, Age Factors, Brain, Parkinson Disease, Genomics, medicine.disease, 3. Good health, Europe, 030104 developmental biology, Conceptual framework, Ageing, Geriatrics, Research Design, Case-Control Studies, Nerve Degeneration, Twin Studies as Topic, Female, Healthy ageing, Inflammation Mediators, business, 030217 neurology & neurosurgery, Motor disability, Developmental Biology, Signal Transduction
Abstract

Advanced age is the major risk factor for idiopathic Parkinson's disease (PD), but to date the biological relationship between PD and ageing remains elusive. Here we describe the rationale and the design of the H2020 funded project "PROPAG-AGEING", whose aim is to characterize the contribution of the ageing process to PD development. We summarize current evidences that support the existence of a continuum between ageing and PD and justify the use of a Geroscience approach to study PD. We focus in particular on the role of inflammaging, the chronic, low-grade inflammation characteristic of elderly physiology, which can propagate and transmit both locally and systemically. We then describe PROPAG-AGEING design, which is based on the multi-omic characterization of peripheral samples from clinically characterized drug-naive and advanced PD, PD discordant twins, healthy controls and "super-controls", i.e. centenarians, who never showed clinical signs of motor disability, and their offspring. Omic results are then validated in a large number of samples, including in vitro models of dopaminergic neurons and healthy siblings of PD patients, who are at higher risk of developing PD, with the final aim of identifying the molecular perturbations that can deviate the trajectories of healthy ageing towards PD development.

Published
2020
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