Biomarkers of dementia in the general population
Prof. Dr. Hans Jörgen Grabe
Group Leader
Ellernholzstr. 1-2
17489 Greifswald

hans.grabe@dzne.de
 +49 3834 86-6915

Areas of investigation/research focus

1.           Genetic factors in Dementia

At the University Medicine of Greifswald we have extensive clinical phenotype data and whole body MRI-images from the population-based cohorts SHIP and TREND (SHIP/TREND, n> 8000) and inpatients cohorts (GANI_MED, n>4500).

We coordinate the German activities in the JPND project “Brain Imaging, cognition, Dementia and next generation GEnomics: a Transdisciplinary approach to search for risk and protective factors of neurodegenerative disease” (BRIDGET). Together with international partners, we search for common and rare genetic variants of AD and will establish new brain imaging markers for early risk assessment of dementia. Additionally, we perform genome-wide sequencing for the determination of the degree of methylation (Methyl-C sequencing).

Along with the molecular parameters clinical and brain imaging phenotypes will be analysed.My group is responsible for new structural MRI markers (see 2.)

 more Infos

2.           Novel MRI markers of ageing

Based on previous neuroimaging studies we applied a high-dimensional pattern classification to calculate spatial pattern of abnormality for recognition of early Alzheimer’s Disease (SPARE-AD) and similarly used this machine learning methodology for quantifying brain ageing-related atrophy patterns in SHIP subjects (SPARE-BA). These scores are now used in biomarker research for early AD.

3.           Urine Metabolomics in Dementia

Based on NMR-measured urine metabolites we have established a metabolic age score indicating biological ageing as departure from chronological age. As part of this research we have identified metabolites that are associated with ageing and gray matter loss in the brain. These metabolites will be tested in special ageing cohorts (e.g. DELCODE) for their association to Alzheimer´s disease.

Schlüsselpublikationen

Hans Jörgen Grabe, Katharina Wittfeld, Sandra van der Auwera, Deborah Janowitz, Katrin Hegenscheid, Mohamad Habes, Georg Homuth, Sven Barnow, Ulrich John, Matthias Nauck, Henry Völzke, Henriette Meyer zu Schwabedissen, Harald Jürgen Freyberger, Norbert Hosten. Effect of the interaction between childhood abuse and rs1360780 of the FKBP5 gene on gray matter volume in a general population sample. Human Brain Mapping. 2016 Mar 31; 37:1602-1613. doi: 10.1002/hbm.23123
Johannes Hertel, Nele Friedrich, Katharina Wittfeld, Maik Pietzner, Kathrin Budde, Sandra Van Der Auwera, Tobias Lohmann, Alexander Teumer, Henry Völzke, Matthias Nauck, Hans Jörgen Grabe. Measuring Biological Age via Metabonomics: The Metabolic Age Score. Journal of Proteome Research. 2016 Feb 04; 15:400-410. doi: 10.1021/acs.jproteome.5b00561
Mohamad Habes, Guray Erus, Jon B. Toledo, Tianhao Zhang, Nick Bryan, Lenore J. Launer, Yves Rosseel, Deborah Janowitz, Jimit Doshi, Sandra Van Der Auwera, Bettina Von Sarnowski, Katrin Hegenscheid, Norbert Hosten, Georg Homuth, Henry Völzke, Ulf Schminke, Wolfgang Hoffmann, Hans J. Grabe, Christos Davatzikos. White matter hyperintensities and imaging patterns of brain ageing in the general population. Brain. 2016 Mar 31; 139:1164-1179. doi: 10.1093/brain/aww008
Deborah Janowitz, Katharina Wittfeld, Jan Terock, Harald Jürgen Freyberger, Katrin Hegenscheid, Henry Völzke, Mohamad Habes, Norbert Hosten, Nele Friedrich, Matthias Nauck, Grazyna Domanska, Hans Jörgen Grabe. Association between waist circumference and gray matter volume in 2344 individuals from two adult community-based samples. NeuroImage. 2015 Nov 04; 122:149-157. doi: 10.1016/j.neuroimage.2015.07.086
Derrek P. Hibar, Jason L. Stein, Miguel E. Renteria, Alejandro Arias-Vasquez, Sylvane Desrivières, Neda Jahanshad, Roberto Toro, Katharina Wittfeld, Lucija Abramovic, Micael Andersson, Benjamin S. Aribisala, Nicola J. Armstrong, Manon Bernard, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Andrew A. Brown, Mallar Chakravarty, Qiang Chen, Christopher R. K. Ching, Gabriel Cuellar-Partida, Anouk Den Braber, Sudheer Giddaluru, Aaron L. Goldman, Oliver Grimm, Tulio Guadalupe, Johanna Hass, Girma Woldehawariat, Avram J. Holmes, Martine Hoogman, Deborah Janowitz, Tianye Jia, Sungeun Kim, Marieke Klein, Bernd Kraemer, Phil H. Lee, Loes M. Olde Loohuis, Michelle Luciano, Christine MacAre, Karen A. Mather, Manuel Mattheisen, Yuri Milaneschi, Kwangsik Nho, Martina Papmeyer, Adaikalavan Ramasamy, Shannon L. Risacher, Roberto Roiz-Santiañez, Emma J. Rose, Alireza Salami, Philipp G. Sämann, Lianne Schmaal, Andrew J. Schork, Jean Shin, Lachlan T. Strike, Alexander Teumer, Marjolein M. J. Van Donkelaar, Kristel R. Van Eijk, Raymond K. Walters, Lars T. Westlye, Christopher D. Whelan, Anderson M. Winkler, Marcel P. Zwiers, Saud Alhusaini, Lavinia Athanasiu, Stefan Ehrlich, Marina M. H. Hakobjan, Cecilie B. Hartberg, Unn K. Haukvik, Angelien J. G. A. M. Heister, David Hoehn, Dalia Kasperaviciute, David C. M. Liewald, Lorna M. Lopez, Remco R. R. Makkinje, Mar Matarin, Marlies A. M. Naber, Reese McKay, Margaret Needham, Allison C. Nugent, Benno Pütz, Natalie A. Royle, Li Shen, Emma Sprooten, Daniah Trabzuni, Saskia S. L. Van Der Marel, Kimm J. E. Van Hulzen, Esther Walton, Christiane Wolf, Laura Almasy, David Ames, Sampath Arepalli, Amelia A. Assareh, Mark E. Bastin, Henry Brodaty, Kazima B. Bulayeva, Melanie A. Carless, Sven Cichon, Aiden Corvin, Joanne E. Curran, Michael Czisch, Greig I. De Zubicaray, Allissa Dillman, Ravi Duggirala, Thomas D. Dyer, Susanne Erk, Iryna O. Fedko, Luigi Ferrucci, Tatiana M. Foroud, Peter T. Fox, Masaki Fukunaga, Raphael Gibbs, Harald H. H. Göring, Robert C. Green, Sebastian Guelfi, Narelle K. Hansell, Catharina A. Hartman, Katrin Hegenscheid, Andreas Heinz, Dena G. Hernandez, Dirk J. Heslenfeld, Pieter J. Hoekstra, Florian Holsboer, Georg Homuth, Jouke-Jan Hottenga, Masashi Ikeda, Clifford R. Jack, Mark Jenkinson, Robert Johnson, Ryota Kanai, Maria Keil, Jack W. Kent, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Xinmin Liu, Dan L. Longo, Katie L. McMahon, Eva Meisenzahl, Ingrid Melle, Sebastian Mohnke, Grant W. Montgomery, Jeanette C. Mostert, Thomas W. Mühleisen, Michael A. Nalls, Thomas E. Nichols, Lars G. Nilsson, Markus M. Nöthen, Kazutaka Ohi, Rene L. Olvera, Rocio Perez-Iglesias, Bruce Pike, Steven G. Potkin, Ivar Reinvang, Simone Reppermund, Marcella Rietschel, Nina Romanczuk-Seiferth, Glenn D. Rosen, Dan Rujescu, Knut Schnell, Peter R. Schofield, Colin Smith, Vidar M. Steen, Jessika E. Sussmann, Anbupalam Thalamuthu, Arthur W. Toga, Bryan J. Traynor, Juan Troncoso, Jessica A. Turner, Maria C. Valdés Hernández, Dennis Van 'T Ent, Marcel Van Der Brug, Nic J. A. Van Der Wee, Marie-Jose Van Tol, Dick J. Veltman, Thomas H. Wassink, Eric Westman, Ronald H. Zielke, Alan B. Zonderman, David G. Ashbrook, Reinmar Hager, Lu Lu, Francis J. McMahon, Derek W. Morris, Robert W. Williams, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Wiepke Cahn, Vince D. Calhoun, Gianpiero L. Cavalleri, Benedicto Crespo-Facorro, Anders M. Dale, Gareth E. Davies, Norman Delanty, Chantal Depondt, Srdjan Djurovic, Wayne C. Drevets, Thomas Espeseth, Randy L. Gollub, Beng-Choon Ho, Wolfgang Hoffmann, Norbert Hosten, René S. Kahn, Stephanie Le Hellard, Andreas Meyer-Lindenberg, Bertram Müller-Myhsok, Matthias Nauck, Lars Nyberg, Massimo Pandolfo, Brenda W. J. H. Penninx, Joshua L. Roffman, Sanjay M. Sisodiya, Jordan W. Smoller, Hans Van Bokhoven, Neeltje E. M. Van Haren, Henry Völzke, Henrik Walter, Michael W. Weiner, Wei Wen, Tonya White, Ingrid Agartz, Ole A. Andreassen, John Blangero, Dorret I. Boomsma, Rachel M. Brouwer, Dara M. Cannon, Mark R. Cookson, Eco J. C. De Geus, Ian J. Deary, Gary Donohoe, Guillén Fernández, Simon E. Fisher, Clyde Francks, David C. Glahn, Hans J. Grabe, Oliver Gruber, John Hardy, Ryota Hashimoto, Hilleke E. Hulshoff Pol, Erik G. Jönsson, Iwona Kloszewska, Simon Lovestone, Venkata S. Mattay, Patrizia Mecocci, Colm McDonald, Andrew M. McIntosh, Roel A. Ophoff, Tomas Paus, Zdenka Pausova, Mina Ryten, Perminder S. Sachdev, Andrew J. Saykin, Andy Simmons, Andrew Singleton, Hilkka Soininen, Joanna M. Wardlaw, Michael E. Weale, Daniel R. Weinberger, Hieab H. H. Adams, Lenore J. Launer, Stephan Seiler, Reinhold Schmidt, Ganesh Chauhan, Claudia L. Satizabal, James T. Becker, Lisa Yanek, Sven J. Van Der Lee, Maritza Ebling, Bruce Fischl, Longstreth, Douglas Greve, Helena Schmidt, Paul Nyquist, Louis N. Vinke, Cornelia M. Van Duijn, Luting Xue, Bernard Mazoyer, Joshua C. Bis, Vilmundur Gudnason, Sudha Seshadri, M. Arfan Ikram, Nicholas G. Martin, Margaret J. Wright, Gunter Schumann, Barbara Franke, Paul M. Thompson, Sarah E. Medland. Common genetic variants influence human subcortical brain structures. Nature. 2015 Apr 08; 520:224-229. doi: 10.1038/nature14101

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