Understanding the way that Alzheimer’s disease cripples the brain and then designing an affordable treatment is what drives the work of Jürgen Götz, PhD.
His ideas to combine focused ultrasound, immunology, and medications are leading to big discoveries, as we reported earlier this year. To learn more about the scientist behind these exciting advances in Alzheimer’s disease treatment, we interviewed University of Queensland Professor Jürgen Götz, PhD, about his ongoing work, collaborations, and achievements.
Focused Ultrasound Work
Q. When and how did you get interested in FUS?
Driven by mere curiosity, after my decision to relocate to the University of Queensland, I decided to get a system and contacted Dr. Elisa Konofagou in November 2011 after her paper came out in the Proceedings of the National Academy of Sciences. We ordered the Philips research system in March 2012.
Q. What are your areas of interest in FUS?
Alzheimer’s disease and related proteinopathies.
Q. What mechanisms and clinical indications do you study?
Amyloid clearance in the absence of therapeutic agents and tau clearance in combination with tau-specific antibodies.
Q. What is the goal of your work?
Only a fraction of my lab works on therapeutic strategies. Most members of my team work on projects to understand pathogenic mechanisms in Alzheimer’s disease and frontotemporal dementia. Regarding therapies, our goal is to find an affordable treatment for Alzheimer’s disease, combining pharmacological with non-pharmacological approaches.
Q. What are your funding sources?
Governmental funding agencies (National Health and Medical Research Council, Australian Research Council), State and Commonwealth, and philanthropic organizations (such as the Clem Jones Foundation).
Q. What comes next?
We have started safety studies in sheep, the application of scanning ultrasound (SUS) to murine models with a tau pathology, and additional studies into the role of glia in ultrasound-mediated amyloid clearance.
Research Site Information
Q. What is the name of your research institute, and where is it located?
The Clem Jones Centre for Ageing Dementia Research is based at the Queensland Brain Institute, which is located at the University of Queensland in Australia.
Q. What is the name of your laboratory?
The Götz Laboratory
Q. When was your laboratory started, who started it, and why?
I published my first Alzheimer’s-related paper in 1995. The laboratory was set up in 2012.
Q. What are your projects?
The major focus of the laboratory is to understand pathomechanisms in neurodegenerative diseases, such as Alzheimer’s, and develop treatment strategies for them.
Q. Who are your team members?
The other team leaders from the CJCADR are listed on our website. The scientists in my laboratory who are currently working on ultrasound-related projects include Gerhard Leinenga, Rebecca Nisbet, Ann van der Jeugd, Matthew Plekanos, and Rob Hatch.
Q. Who are your internal and external collaborators?
I have a long-standing collaboration with Prof. Eckert from Basel, a world expert in oxidative stress and mitochondrial assays. I have established collaborations with prominent neuropathologists at the University of Cologne, the University of New South Wales, and the University of Sydney. I am also collaborating with Prof. Mel Feany, a leading Drosophila geneticist at Harvard University.
Q. What are your grea achievements?
At the beginning of my career, I contributed mainly to developmental biology. Since 1994, I have focused my career on neurodegenerative research, making major contributions to the field such as:
- Proving the amyloid cascade hypothesis (Science 2001)
- Aβ toxicity is tau-dependent – a paradigm shift in the field (Cell 2010)
- Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model – a new treatment strategy (Science Transl Med 2015)
Q. Have you worked with the Foundation?
Together with my PhD student Gerhard Leinenga, I attended the Foundation’s Alzheimer’s workshop in Washington last month. This excellent event helped us to network with other researchers in the field (including those who had led the foundation of ultrasound-mediated BBB opening for therapy).
Q. How many patients have you treated?
I am not a clinician, but we are increasingly working together with clinicians.
New Pre-Clinical Research Further Validates Potential for Focused Ultrasound in Alzheimer’s June 2015
Study Suggests Focused Ultrasound May Help Unlock Alzheimer’s March 2015
Leinenga G, Götz J Scanning Ultrasound Efficiently Removes Amyloid-β and Restores Memory in an Alzheimer’s Disease Mouse Model. Science Transl Med 11:276ra33. Impact factor of 15.843 [Cover image] [Highlighted in Science 347: 1186-87, 2015] [Highlighted in Nature Rev Neurol 11: 247, 2015] (2 cit.)
Ittner LM, Ke YD, Delerue F, et al. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell 2010;142(3):387-397. doi: 310.1016/j.cell.2010.1006.1036.
Ferrari A, Hoerndli F, Baechi T, Nitsch RM, Gotz J. beta-Amyloid induces paired helical filament-like tau filaments in tissue culture. J Biol Chem 2003;278(41):40162-40168.
Götz J, Chen F, Barmettler R, Nitsch RM. Tau Filament Formation in Transgenic Mice Expressing P301L Tau. J Biol Chem January 5, 2001 2001;276(1):529-534.
Gotz J, Chen F, van Dorpe J, Nitsch RM. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science 2001;293(5534):1491-1495. This publication provided long-sought evidence for the amyloid cascade hypothesis by combining a transgenic and a transplantation approach, is highly cited, was accompanied by an Editorial in the same issue of Science, and was selected as Milestone Paper by Alzforum.
Gotz J, Probst A, Spillantini MG, et al. Somatodendritic localization and hyperphosphorylation of tau protein in transgenic mice expressing the longest human brain tau isoform. Embo J 1995;14(7):1304-1313.