Redefining Alzheimer’s disease
Projectomschrijving
Mensen met Alzheimer verschillen van elkaar. De ene persoon krijgt de ziekte op zijn 50e, de ander pas op zijn 90e. Dit betekent dat Alzheimer niet 1 ziekte is, maar dat er verschillende subtypes zijn met verschillende oorzaken.
Doel
Het doel van deze studie is om deze verschillende subtypes in kaart te brengen, omdat er waarschijnlijk ook verschillende behandelingen voor nodig zijn.
Aanpak
Eiwitten in het hersenvocht laten zien wat er in de hersenen gebeurt. Door analyse van eiwitpatronen willen de onderzoekers de verschillende oorzaken van Alzheimer-subtypes opsporen. Ook wordt onderzocht of deze eiwitpatronen samenhangen met erfelijke aanleg, levensstijl, de leeftijd waarop de ziekte begint en de snelheid van achteruitgang. Tenslotte wordt onderzocht hoe mensen reageren op een behandeling die past bij de onderliggende oorzaak van het subtype. Hiervoor wordt onder andere hersenvocht gebruikt van mensen die meededen aan eerdere studies. De nieuwe kennis leidt tot betere diagnostiek en behandeling.
Meer informatie
Producten
Auteur: Elles Konijnenberg1, Betty M. Tijms1, Charlotte E. Teunissen2, Robert Veerhuis2,3, August B Smit4, Philip Scheltens1, Pieter Jelle Visser1,5*, for the Alzheimer’s Disease Neuroimaging Initiative
Auteur: Betty M. Tijms1*, Charlotte E. Teunissen2, Philip Scheltens1, and Pieter Jelle Visser1,3 for the Alzheimer’s Disease Neuroimaging Initiative
Link: https://adpd.kenes.com/2019
Auteur: BMT Tijms
Link: https://adpd2022.kenes.com/
Auteur: E Vroomen
Link: https://aaic.alz.org/highlights2022.asp
Auteur: Elles Konijnenberg1, Betty M. Tijms1*, Charlotte E. Teunissen2, Robert Veerhuis2,3, August B Smit4, Philip Scheltens1, Pieter Jelle Visser1,5, for the Alzheimer’s Disease Neuroimaging Initiative** * presenting author.
Link: http://www.neurochem.info/html/meeting
Auteur: Kirsten Wesenhagen, PJ Visser, Philip Scheltens, Charlotte Teunissen, Betty Tijms.
Link: https://adpd.kenes.com/2019/submit-your-abstract/junior-faculty-awards
Auteur: Marta Del Campo, Carel F.W. Peeters, Erik C.B. Johnson, Lisa Vermunt, Yanaika S. Hok-A-Hin, Mirrelijn van Nee, Alice Chen-Plotkin, William T. Hu, James J. Lah, Nicholas T. Seyfried, Gonzalo Herradon, Lieke H.H. Meeter, John C. van Swieten, Allan I. Levey, Afina W. Lemstra, Yolande A.L. Pijnenburg, Pieter Jelle Visser, Betty M. Tijms, Wiesje M van der Flier, Charlotte E. Teunissen …
Auteur: Betty Tijms, Johan Gobom, Kaj Blennow, Magda Tsolaki , Frans RJ Verhey , Julius Popp, Pablo Martinez Lage, Rik Vandenberghe, Alberto Lleo, Sebastiaan Engelborghs, José Luís Molinuevo, Lars Bertram, Simon Lovestone, Johannes Streffer, Stephanie Vos, Bos Isabelle , Charlotte E. Teunissen, Philip Scheltens, Henrik Zetterberg, and Pieter Jelle Visser.
Link: https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1016/j.jalz.2019.06.2649
Auteur: PJ Visser
Link: https://eurotau.fr/
Auteur: PJ Visser
Link: https://adpd2022.kenes.com/
Auteur: Lianne Reus
Link: https://aaic.alz.org/highlights2022.asp
Auteur: Pieter Jelle Visser, Jori Tomassen, Anouk den Braber, Dorret I Boomsma, Marta Del Campo, Maqsood Yaqub, Bart NM Van Berckel, Philip Scheltens, Charlotte E. Teunissen, Betty M Tijms
Auteur: Kirsten E.J. Wesenhagen, Pieter Jelle Visser, Johan Gobom, Isabelle Bos, Stephanie J.B. Vos, Pablo Martinez-Lage, Mikel Tainta, Julius Popp, Gwendoline Peyratout, Magda Tsolaki, Rik Vandenberghe, Yvonne Freund-Levi, Frans R.J. Verhey, Prof. Simon Lovestone, Johannes Streffer, Kaj Blennow, Philip Scheltens, Charlotte E. Teunissen, Henrik Zetterberg, Betty M. Tijms, Alzheimer’s Disease Neuroimaging Initiative
Auteur: Kirsten Wesenhagen, PJ Visser, C Teunissen, B Tijms.
Link: http://www.neurochem.info/html/meeting
Auteur: Pieter Jelle Visser, Johan Gobom, Lianne M. Reus, Iris E. Jansen, Magda Tsolaki, Frans R.J. Verhey, Julius Popp, Pablo Martinez-Lage, Rik Vandenberghe, Alberto Lleó, Jose Luis Molinuevo, Sebastiaan Engelborghs, Simon Lovestone, Johannes Streffer, Stephanie J.B. Vos, Isabelle Bos, Lars Bertram, Danielle Posthuma, August B. Smit, Kaj Blennow, Philip Scheltens, Charlotte E. Teunissen, Henrik Zetterberg, Betty M. Tijms
Link: https://alz-journals.onlinelibrary.wiley.com/doi/abs/10.1016/j.jalz.2019.08.072
Auteur: BMT Tijms
Auteur: BMT Tijms
Auteur: Lianne M. Reus, Iris E. Jansen, Betty M. Tijms, Pieter Jelle Visser, Afina W. Lemstra, Yolande A.L. Pijnenburg, Wiesje van Der Flier, Charlotte E. Teunissen, Marta Del Campo
Auteur: BMT Tijms
Link: https://aaic.alz.org/highlights2022.asp
Auteur: BMT Tijms, K Wesenhagen, Ch Teunissen, F Berve, Ph Scheltens, Pj Visser
Link: https://www.vibconferences.be/events/new-horizons-in-alzheimers-disease
Auteur: PJ Visser
Link: https://aaic.alz.org/highlights2022.asp
Auteur: Pieter Jelle Visser, Lianne M. Reus, Johan Gobom, Iris Jansen, Ellen Dicks, Sven J. van der Lee, Magda Tsolaki, Frans R. J. Verhey, Julius Popp, Pablo Martinez-Lage, Rik Vandenberghe, Alberto Lleó, José Luís Molinuevo, Sebastiaan Engelborghs, Yvonne Freund-Levi, Lutz Froelich, Kristel Sleegers, Valerija Dobricic, Simon Lovestone, Johannes Streffer, Stephanie J. B. Vos, Isabelle Bos, ADNI, August B. Smit, Kaj Blennow, Philip Scheltens, Charlotte E. Teunissen, Lars Bertram, Henrik Zetterber
Magazine: Molecular neurodegeneration
Link: https://pubmed.ncbi.nlm.nih.gov/35346299/
Auteur: Kirsten E.J. Wesenhagen Johan Gobom Isabelle Bos Stephanie J.B. Vos Pablo Martinez-Lage Julius Popp Magda Tsolaki Rik Vandenberghe Yvonne Freund-Levi Frans Verhey Simon Lovestone Johannes Streffer, Valerija Dobricic Lars Bertram for the Alzheimer’s Disease Neuroimaging Initiative Kaj Blennow Maria Pikkarainen20 Merja Hallikainen Johanna Kuusist, Markku Laakso, Hilkka Soininen, Philip Scheltens,Henrik Zetterberg Charlotte E. Teunissen Pieter Jelle Visser Betty M. Tijms
Magazine: Alzheimer's & Dementia
Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9074716/
Auteur: Pieter Jelle Visser, Lianne M Reus, Johan Gobom, Iris Jansen, Ellen Dicks, Magda Tsolaki, Frans R J Verhey, Julius Popp, Pablo Martinez-Lage, Rik Vandenberghe, Alberto Lleó, José Luís Molinuevo, Sebastiaan Engelborghs, Yvonne Freund-Levi, Lutz Froelich, Kristel Sleegers, Valerija Dobricic, Shengjun Hong, Simon Lovestone, Johannes Streffer, Stephanie J B Vos, Isabelle Bos, August B Smit, Kaj Blennow, Philip Scheltens, Charlotte E Teunissen, Lars Bertram, Henrik Zetterberg, Betty M Tijms
Magazine: medRxiv
Auteur: Kirsten E J Wesenhagen, Betty M Tijms, Lynn Boonkamp, Patty L Hoede , Julie Goossens, Nele Dewit, Philip Scheltens, Eugeen Vanmechelen, Pieter Jelle Visser , Charlotte E Teunissen
Magazine: Alzheimer's research & therapy
Auteur: Flora H. Duits, Kirsten E. J. Wesenhagen, Laura Ekblad, Emma Wolters, Eline A. J. Willemse, ADNI, Philip Scheltens, Wiesje M. van der Flier, Charlotte E. Teunissen, Pieter Jelle Visser & Betty M. Tijms
Magazine: Alzheimer's research & therapy
Link: https://alzres.biomedcentral.com/articles/10.1186/s13195-020-00713-3
Auteur: Konijnenberg, Elles, Tijms, Betty M., Gobom, Johan, Dobricic, Valerija, Bos, Isabelle, Vos, Stephanie, Tsolaki, Magda, Verhey, Frans, Popp, Julius, Martinez-Lage, Pablo, Vandenberghe, Rik, Lleó, Alberto, Frölich, Lutz, Lovestone, Simon, Streffer, Johannes, Bertram, Lars, Blennow, Kaj, Teunissen, Charlotte E., Veerhuis, Robert, Smit, August B., Scheltens, Philip, Zetterberg, Henrik, Visser, Pieter Jelle
Magazine: Alzheimer's research & therapy
Auteur: Sophia Weiner, Mathias Sauer , Pieter Jelle Visser, Betty M Tijms, Egor Vorontsov, Kaj Blennow, Henrik Zetterberg, Johan Gobom
Magazine: clinical proteomics
Link: https://clinicalproteomicsjournal.biomedcentral.com/
Auteur: Hazal Haytural, Rui Benfeitas, Sophia Schedin-Weiss, Erika Bereczki, Melinda Rezeli, Richard D. Unwin, Xusheng Wang, Eric B. Dammer, Erik C. B. Johnson, Nicholas T. Seyfried, Bengt Winblad, Betty M. Tijms, Pieter Jelle Visser, Susanne Frykman & Lars O. Tjernberg
Magazine: Scientific data
Link: https://www.nature.com/articles/s41597-021-01090-8
Auteur: Flora H Duits, Kirsten E J Wesenhagen , Laura Ekblad , Emma Wolters , Eline A J Willemse , ADNI; Philip Scheltens , Wiesje M van der Flier , Charlotte E Teunissen , Pieter Jelle Visser , Betty M Tijms
Magazine: Alzheimer's research & therapy
Auteur: Aurore Delvenne Johan Gobom Betty Tijms Isabelle Bos Lianne M. Reus Valerija Dobricic Mara ten Kate Frans Verhey Inez Ramakers Philip Scheltens Charlotte E. Teunissen Rik Vandenberghe Jolien Schaeverbeke Silvy Gabel Julius Popp Gwendoline Peyratou Pablo Martinez-Lage Mikel Tainta Magda Tsolaki Yvonne Freund-Levi Simon Lovestone Johannes Streffer Frederik Barkhof Lars Bertram Kaj Blennow Henrik Zetterberg Pieter Jelle Visser Stephanie J. B. Vos
Magazine: Alzheimer's & Dementia
Link: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12713
Auteur: Betty M Tijms , Johan Gobom , Lianne Reus , Iris Jansen 1, Shengjun Hong , Valerija Dobricic , Fabian Kilpert , Mara Ten Kate , Frederik Barkhof , Magda Tsolaki 7, Frans R J Verhey , Julius Popp , Pablo Martinez-Lage 1 , Rik Vandenberghe , Alberto Lleó , José Luís Molinuevo , Sebastiaan Engelborghs , Lars Bertram , Simon Lovestone , Johannes Streffer , Stephanie Vos , Isabelle Bos , Alzheimer’s Disease Neuroimaging Initiative (ADNI); Kaj Blennow , Philip Scheltens
Magazine: Brain
Auteur: Aurore Delvenne Johan Gobom Betty Tijms Isabelle Bos Lianne M. Reus Valerija Dobricic Mara ten Kate Frans Verhey Inez Ramakers Philip Scheltens Charlotte E. Teunissen Rik Vandenberghe Jolien Schaeverbeke Silvy Gabel Julius Popp Gwendoline Peyratou Pablo Martinez-Lage Mikel Tainta Magda Tsolaki Yvonne Freund-Levi Simon Lovestone Johannes Streffer Frederik Barkhof Lars Bertram Kaj Blennow Henrik Zetterberg Pieter Jelle Visser Stephanie J. B. Vos
Magazine: Alzheimer's & Dementia
Link: https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.12713
Auteur: Wesenhagen, Kirsten E. J., Teunissen, Charlotte E., Visser, Pieter Jelle, Tijms, Betty M.
Magazine: Critical Reviews in Clinical Laboratory Sciences
Link: https://www.tandfonline.com/doi/full/10.1080/10408363.2019.1670613
Auteur: Eleonora M Vromen , Marta Del Campo Milán, Philip Scheltens , Charlotte E Teunissen , Pieter Jelle Visser , Betty M Tijms
Magazine: Alzheimer's research & therapy
Link: https://pubmed.ncbi.nlm.nih.gov/35229020/
Auteur: Laura L Ekblad , Pieter Jelle Visser , Betty M Tijms , Alzheimer´s Disease Neuroimaging Initiative
Magazine: Neurobiology of Aging
Link: https://www.sciencedirect.com/science/article/pii/S019745802100227X?via%3Dihub
Auteur: Catherine Schramm, Camille Charbonnier, Aline Zaréa , Morgane Lacour2 , David Wallon , CNRMAJ collaborators, Anne Boland , Jean-François Deleuze , Robert Olaso , ADES consortium, Flora Alarcon4 , Dominique Campion1, Grégory Nuel 6and Gaël Nicolas1*
Magazine: Genome medicine
Link: https://genomemedicine.biomedcentral.com/articles/10.1186/s13073-022-01070-6
Auteur: Iris E Jansen, Sven J van der Lee, Duber Gomez-Fonseca, Itziar de Rojas, Maria C Dalmasso, Benjamin Grenier-Boley, Anna Zettergren, Aniket Mishra, Muhammad Ali, Victor Andrade, Céline Bellenguez, Luca Kleineidam, Fahri Küçükali, Yun Ju Sung, Niccolo Tesí, Ellen M Vromen, Douglas P Wightman, Daniel Alcolea, Montserrat Alegret, Ignacio Alvarez, Philippe Amouyel, Lavinia A Andresen, Shahram Bahrami, Henri Bailly, Olivia Belbin, Sverre Bergh, Geert Jan Biessels, Kaj Blennow, Rafael Bl
Magazine: medRxiv
Link: http://www.medrxiv.org/content/10.1101/2022.03.08.22271043v1
Auteur: Richeng Jiang, Una Smailovic, Hazal Haytural, Betty M. Tijms, Hao Li, Robert Mihai Haret, Ganna Shevchenko, Gefei Chen, Axel Abelein, Johan Gobom, Susanne Frykman, Misaki Sekiguchi, Ryo Fujioka, Naoto Watamura, Hiroki Sasaguri, Sofie Nyström, Per Hammarström, Takaomi C. Saido, Vesna Jelic, Stina Syvänen, Henrik Zetterberg, Bengt Winblad, Jonas Bergquist, Pieter Jelle Visser & Per Nilsson
Magazine: Acta Neuropathologica communications
Link: https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-022-01398-5
Auteur: Reus, Lianne M., Stringer, Sven, Posthuma, Danielle, Teunissen, Charlotte E., Scheltens, Philip, Pijnenburg, Yolande A.L., Visser, Pieter Jelle, Tijms, Betty M.
Magazine: Neurobiology of Aging
Auteur: Eleonora M Vromen 1 2 , Sterre C M de Boer 1 2 , Charlotte E Teunissen 3 , Annemieke Rozemuller, Anne Sieben, Maria Bjerke , Alzheimer’s Disease Neuroimaging Initiative; Pieter Jelle Visser , Femke H Bouwman , Sebastiaan Engelborghs , Betty M Tijms
Magazine: Brain
Link: https://doi.org/10.1093/brain/awac158
Auteur: Betty Marije Tijms , Johan Gobom , Charlotte Teunissen , Valerija Dobricic , Magda Tsolaki , Frans Verhey , Julius Popp , Pablo Martinez-Lage , Rik Vandenberghe, Alberto Lleó , José Luís Molinuévo , Sebastiaan Engelborghs , Yvonne Freund-Levi , Lutz Froelich, Lars Bertram , Simon Lovestone, Johannes Streffer, Stephanie Vos , ADNI ‡, Kaj Blennow Philip Scheltens , Henrik Zetterberg and Pieter Jelle Visser
Magazine: proteomes
Link: https://www.mdpi.com/2227-7382/9/3/36
Auteur: Roos J. Jutten, PhD, Sietske A.M. Sikkes, PhD, Wiesje M. Van der Flier, PhD, Philip Scheltens, MD, PhD, Pieter Jelle Visser, MD, PhD, and Betty M. Tijms, PhD, for the Alzheimer’s Disease Neuroimaging Initiative
Magazine: Neurology
Auteur: PJ Visser and BM Tijms
Auteur: Visser, Tijms, Zetterberg, Blennow
Link: https://patents.google.com/patent/US20220196683A1/en
Verslagen
Samenvatting van de aanvraag
The current definition of Alzheimer’s disease (AD) considers the disease as a single entity. However, genetic studies have demonstrated that AD is a heterogeneous disorder. This poses a major hurdle for drug development as subtypes of AD may exist that need different treatments. It is not yet possible to identify such subtypes. We propose to develop a novel, biologically informed definition of AD subtypes based on underlying pathophysiology using cerebrospinal fluid (CSF) proteomics. CSF proteomics provide the most direct way to measure biological processes in the brain in vivo. Measurement of single proteins demonstrated the power of CSF analysis for detecting amyloid pathology and neuronal injury. Recently, novel high throughput assays have made it possible to measure over 1000 proteins at the same time, which now enables to assess many other pathophysiological processes involved in the development of the disease. We now propose to use this new technique to define subtypes through data driven analysis of the CSF proteome. In a pilot study we showed the feasibility of our approach and we were able to detect 3 AD subtypes with distinct biological pathway dysfunction. We will now apply this technique to over 1500 subjects selected from our own studies, and from our international collaborations. This will make our study the world’s largest AD CSF proteomic study to date. We have four aims: 1) Identify ‘proteomic signatures’ of AD pathophysiological subtypes through unbiased data-mining analysis of 1305 proteins in already collected cerebrospinal fluid samples from 650 subjects; 2) Develop proteomic signature scores for AD subtypes that allow for diagnosis and for tracking disease progression; 3) Characterise subtypes in terms of: genetic and non-genetic risk-factors, change over time, clinical and neuroimaging markers and specificity for AD; 4) Test the influence of AD subtype to treatment response using CSF samples from previous AD trials. Through our collaborations we can thoroughly assess the robustness of our results by externally replicating all analyses using independent proteomic data (total n across studies = 970). This study will deliver much-needed new insights in AD pathophysiology that will advance the diagnosis and treatment of AD. Our proteomic signature scores can be used to detect distinct pathophysiological subtypes at an individual patient level. This will enable personalised diagnosis, prognosis, and treatment. Our expertise from multiple disciplines, access to large cohorts and state of the art proteomic techniques put us in the unique position to push the field forward.