Jürgen Götz studied biochemistry at the University of Basel, and earned his PhD in immunology in the laboratory of Nobel Laureate Georges Köhler at the Max-Planck-Institute in Freiburg, Germany (1989). After postdoctoral work at UCSF and the Preclinical Research Division at Novartis Ltd in Basel, he established his reputation in the Alzheimer’s field as a research group leader at the University of Zürich (1994–2005). From 2005 - 2011, he has been Chair of Molecular Biology and Director of the Alzheimer’s and Parkinson’s Laboratory at the Brain and Mind Research Institute of the University of Sydney.
In February 2012 he took up the position as Foundation Chair of Dementia Research at The University of Queensland and inaugural director of the Clem Jones Centre for Ageing Dementia Research (CJCADR) at the Queensland Brain Institute (QBI)
It is hard to believe that, despite it being more than a century since the neuropathologist Alois Alzheimer identified the first published case of "presenile dementia", which his colleague Kraepelin would later identify as Alzheimer's disease, there is still no treatment that prevents the relentless neuronal degeneration that is characteristic of this condition. Among Alzheimer’s most important discoveries was the identification of two hallmark brain lesions, amyloid plaques and neurofibrillary tangles. The plaques are made of a small peptide called amyloid-beta, whereas the tangles are composed of the protein tau. Interestingly, as only discovered in the late 1990s, mutations in the genes that encode these proteins do cause inherited forms of dementia. By integrating these histopathological and genetic findings an important implication is that understanding how amyloid-beta and tau cause neurodegeneration is at the heart of finding a cure.
During the past 15 years, my research has focussed on understanding the role of tau and amyloid-beta, and their interaction, in the aetiology of Alzheimer’s disease. A key achievement in this regard was the establishment of the first mouse model with a tau pathology, an essential step in understanding the disease and working towards a cure. As soon as mutations were identified in the gene that encodes tau I expressed these in mice which resulted in more advanced mouse models, including those with authentic neurofibrillary tangle formation. I then correlated tau aggregation with memory impairment, which added to the validity of these models and subsequently helped in validating the efficacy of therapeutic interventions.
In work published in the journal Science I showed that amyloid-beta is upstream of tau. This seminal finding proved the amyloid cascade hypothesis, in essence revealing that reducing amyloid-beta should also abolish the toxic down-stream effects of tau. However, tau is not simply a bystander in this process. In work published in the top journal Cell we showed in 2010 that by modulating or removing tau, the toxicity of amyloid-beta is fully abrogated. In fact, by elucidating the underlying molecular mechanism we developed successful therapeutic strategies in mice.
My other major contributions to the field were discovering how tau pathology causes Parkinsonism, how the cellular power plants, the mitochondria, are impaired by tau and amyloid-beta, and what the relationship is between two pandemic diseases, type 2 diabetes and Alzheimer’s disease. I have also demonstrated in mouse models that sodium selenate, and a tau-based immunisation approach, are viable strategies for the latter condition.
We have established the roundworm C. elegans in the laboratory, an experimental system of less complexity that is used to complement studies in mice and cell lines. My current interest is in understanding the role of tau under both physiological and pathological conditions and in how amyloid-beta and tau interact.
- Dr Mel Feany / Brian DuBoff – Harvard University, USA
- Dr Anne Eckert – University of Basel, Switzerland
- Prof Thomas Ohm - Charite Berlin, Germany
- Prof Hansjörg Schröder/Christoph Köhler – University of Cologne, Germany;
- Prof Ursula Sonnewald – Norwegian University of Science and Technology, Trondheim, Norway
1. DuBoff B, Götz J, Feany M (2012) Tau promotes neurodegeneration via DRP1 mislocalization in vivo, Neuron 75: 618-32 [Highlighted by Cell leading Edge, Cell 151, 7-8, Sep 28, 2012]
2. Schonrock N, Matamales M, Ittner LM, Götz J (2012) miRNA networks surrounding APP and amyloid-β metabolism – Implications for Alzheimer’s disease, Exp Neurol 235(2): 447-54
3. Ke Y, Dramiga Y, Schütz U, Ittner LM, Schröder H, Götz J (2012) Tau mediates cytoplasmic accumulation of the nuclear protein SFPQ in Alzheimer’s disease, PLoS ONE 7(4):e35678 [selected for Faculty of 1000 Biology]
4. Ittner LM, Götz J (2011) Amyloid-β and tau--a toxic pas de deux in Alzheimer's disease, Nature Reviews Neurosci 12: 65-72 [reprinted in Nature 475:S23-S28][translated into German for: Spektrum der Wissenschaft]
5. Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, Wölfing H, Chieng BC, Christie MJ, Napier IA, Eckert A, Staufenbiel M, Hardeman E, Götz J (2010) Dendritic function of tau mediates amyloid-β toxicity in Alzheimer's disease mouse models, Cell 142: 387–97 [discussed in a Perspectives article: Haass C & Mandelkow E (2010) Fyn-Tau-amyloid: a toxic triad. Cell 142: 356-8] [Highlighted in Nature Rev Neurosci, Sep 2010] [Highlighted in Nature Biotechnology, Sep 2010][Selected for Faculty of 1000 Biology]
6. Rhein V, Song X, Wiesner A, Ittner LM, Baysang G, Meier F, Ozmen L, Bluethmann H, Dröse S, Brandt U, Savaskan E, Czech C, Götz J, Eckert A (2009) Amyloid-β and tau synergistically impair the oxidative phosphorylation system in triple transgenic Alzheimer’s disease mice, PNAS 106: 20057-62. [Highlighted in Nature Rev Neurosci, Jan 2010: http://www.nature.com/nrn/journal/v11/n1/pdf/nrn2777.pdf]
7. Ittner LM, Fath T, Ke Y, Bi M, van Eersel J, Li KM, Gunning P and Götz J (2008) Parkinsonism and impaired axonal transport in a mouse model of frontotemporal dementia, Proc Natl Acad Sci USA 105: 15997–16002
8. Götz J, Ittner LM (2008) Animal models of Alzheimer’s disease and frontotemporal dementia, Nature Rev. Neurosci. 9: 532–44 [Featured article, July]
9. Chen F, Wollmer A, Hoerndli F, Münch G, Kuhla B, Rogaev EI, Tsolaki M, Papassotiropoulos A, Götz J (2004) Role for glyoxalase I in Alzheimer’s disease, Proc Natl Acad Sci USA 101: 7687–92
10. Kins S, Crameri A, Evans DRH, Hemmings BA, Nitsch RM, Götz J (2001) Reduced PP2A activity induces abnormal phosphorylation and compartmentalization of tau in transgenic mice, J. Biol. Chem. 276: 38193–38200
11. Götz J, Chen F, van Dorpe J, Nitsch RM (2001) Formation of neurofibrillary tangles in P301L tau transgenic mice induced by Abeta42 fibrils, Science 293: 1491–95