Prof. Dr. Mathias Jucker
Prof. Jucker is board director at the Hertie Institute for Clinical Brain Research
German Center for Neurodegenerative Diseases (DZNE)
+49 (0) 7071 / 29-86863
+49 (0) 7071 / 29-4521
|Dr. Angelos Skodras, Technical Project
|+49 (0) 7071 29-87607||+49 (0) 7071 29-4521|
|Dr. Susanne Gräber-Sultan, Research Associate||+49 (0) 7071 29-81924||+49 (0) 7071 29-4521|
|Sarah Fritschi, Ph.D. student||+49 (0) 7071 29-81945||+49 (0) 7071 29-4521|
|Michael Hruscha, Technical Assistant||+49 (0) 7071 29-86851||+49 (0) 7071 29-4521|
|Marius Lambert, Technical Assistant|
|Tilman König, Study Assistant|
|Elke Kuder-Buletta, Study Assistant|
|Further group members (HIH funding)|
|Renata Novotny, Ph.D. student||+49 (0) 7071 29-81949||+49 (0) 7071 29-4521|
|Lan Ye, Ph.D. student||+49 (0) 7071 29-81949||+49 (0) 7071 29-4521|
Mathias Jucker is a Professor for Cellular Neurology and Director of the Hertie Institute for Clinical Brain Research at the University of Tübingen, Germany.
Professor Jucker studied Neurobiology and did his PhD 1988 at the Swiss Federal Institute of Technology (ETH) Zürich, before he worked as a postdoc and research scientist at the National Institute on Aging, NIH, in Baltimore, USA. He returned to Switzerland as an assistant professor (START fellow) at the University of Basel, and was 2003 called to his current position in Tübingen.
His main areas of research are the cellular and molecular mechanisms responsible for brain aging and Alzheimer’s disease. He has a special interest in cerebral amyloid angiopathies and was first to demonstrate that the lesions in the brain of Alzheimer patients can be induced exogenously by a prion-like mechanism. In addition, he is a member of the Center for Integrative Neurosciences in Tübingen and speaker of the Graduate School of Cellular and Molecular Neuroscience in Tübingen. He is working at DZNE Tübingen since 2009.
Modeling Familial Danish Dementia in mice supports the concept of the amyloid hypothesis of Alzheimer´s disease
Coomaraswamy J, Kilger E, Wölfing H, Schäfer S, Kaeser SA, Wegenast-Braun BM, Hefendehl JK, Wolburg H, Mazzella M, Ghiso J, Goedert M, Akiyama H, Garcia-Sierra F, Wolfer DP, Mathews PM, Jucker M (2010) Proc Natl Acad Sci USA 107:7969-74
Peripherally Applied Aß-Containing Inoculates Induce Cerebral ß-Amyloidosis
Eisele YS, Obermuller U, Heilbronner G, Baumann F, Kaeser SA, Wolburg H, Walker LC, Staufenbiel M, Heikenwalder M, Jucker M (2010) Science 330:980-2
Long-term in vivo imaging of β-amyloid plaque appearance and growth in a mouse model of cerebral β-amyloidosis
Hefendehl JK, Wegenast-Braun BM, Liebig C, Eicke D, Milford D, Calhoun ME, Kohsaka S, Eichner M, Jucker M (2011) J Neurosci 31:624-9
Pathogenic protein seeding in Alzheimer´s disease and other neurodegenerative disorder
Jucker M, Walker LC (2011) Ann Neurol 70:532-40
Soluble Ab seeds are potent inducers of cerebral b-amyloid deposition
Langer F, Eisele YS, Fritschi SK, Staufenbiel M, Walker LC, Jucker M (2011) J. Neuroscience 31:14488-95
The presence of Aβ seeds, and not age per se, is critical to the initiation of Aβ deposition in the brain
Hamaguchi T, Eisele YS, Varvel NH, Lamb BT, Walker LC, Jucker M (2012) Acta Neuropathol 123:31-7
The amyloid state of proteins in human diseases
Eisenberg D, Jucker M (2012) Cell 148:1188-203
Areas of investigation/research focus
Cerebral proteopathy is a unifying term for cerebral neurodegenerative diseases in which aggregated proteins are abnormally deposited in the brain. The hallmark proteopathy is Alzheimer’s disease (AD) in which fibrillar amyloid-β (Aβ) peptide is deposited extracellularly in parenchymal plaques and in the vasculature as cerebral amyloid angiopathy (CAA). Other disorders with cerebral amyloid depositions – albeit of the non-Aß type - include Familial British Dementia, Familial Danish Dementia, and Hereditary Cerebral Hemorrhage with Amyloidosis-Iceland type.
1. To understand how Aβ aggregation is initiated, spreads, and leads to neuronal dysfunction and dementia.
2. To study the mechanism of Aβ-CAA and its contribution to dementia.
3. To study non-Aβ amyloidoses with the objective to identify commonalities and differences to the Aβ-type, which in turn provides insight into disease pathomechanisms.
To this end, we have generated a variety of genetically-engineered mouse models of cerebral amyloidosis of the Aβ- and non-Aβ-type. To foster the translational and therapeutic aspect of our work, results obtained from our mouse models are analyzed in comparison to those in the respective human patient samples.
A hallmark finding from our group is the observation that dilute extracts of Aβ-containing material, from the brains of AD patients or from aged amyloid precursor protein (APP)-transgenic mice, are able to stimulate the induction of β-amyloid deposition and associated lesions in the brains of young APP-transgenic mice. When the Aβ was biochemically inactivated or removed from the brain samples, the extracts lost the ability to induce Aβ-deposition, showing that Aβ itself is necessary for the amyloid induction. Surprisingly, however, synthetic Aβ is much less efficient in inducing the amyloid lesions, suggesting that the ability of Aβ to induce cerebral ß-amyloidosis requires that Aβ molecules acquire certain structural characteristics or co-factors that are generated in the living brain. While these findings bear important similarities to that of prion disease, there is currently no evidence that AD is transmissible in the same sense as are prion diseases. However, the findings indicate that cellular or environmental seeds, in addition to genetic factors, could play a critical role in the initiation of AD (Eisele et al., Science 2010; Langer et al., J Neuroscience 2011; Hamaguchi et al., Acta Neuropathol 2012).
A second recent hallmark accomplishment is the generation of a transgenic mouse model of the rare but fatal Familial Danish Dementia (FDD). The cause of FDD is a defect in the BRI2 gene, which results in the misfolding and accumulation of the ADan protein in the brains of FDD patients. The mouse model, almost identical to the FDD patients, exhibits ADan-amyloid around the walls of blood vessels in form of ADan-CAA, microbleeds, neuroinflammation, and ADan-induced tau pathology (neurofibrillary tangles). Fascinatingly, the disease elicited by the ADan lesions is very similar to that of the Aβ-lesions in AD and Aβ-CAA. These findings suggest common disease mechanisms for FDD and AD. Therapies targeting the amyloid structure of the misfolded proteins may be valuable in the treatment for both FDD and AD (Coomaraswamy et al., PNAS 2010).
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