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Amyloid and Tau in Alzheimer’s Disease

Thursday, January 20, 2022

5:00 PM-6:00 PM

BIOMED Special Topics: Neuroengineering Seminar Series

Amyloid and Tau in Alzheimer’s Disease: From Pathomechanistic Studies Using Super Resolution Microscopy to Therapeutic Ultrasound as a Treatment Modality

Jürgen Götz, PhD
Director of the Clem Jones Center for Aging Dementia Research (CJCADR)
Queensland Brain Institute
Brisbane, Australia

The brain is considered to be the last frontier, both in terms of understanding how it operates under normal and pathological conditions, and in accessing it for therapeutic intervention. My laboratory works in both spaces: deciphering the role of key molecules and signalling pathways in Alzheimer's disease (AD) and developing novel ultrasound-based techniques to overcome the blood-brain barrier (BBB). One of the key features of the AD brain is the deposition of the peptide amyloid-β (Aβ) as plaques and of the protein Tau as tangles, a process that leads to neurodegeneration and dementia.

In the first part of my talk, I will present some of our mechanistic work into how tau and Aβ interact and impair neuronal functions including the translational machinery. The laboratory is further trying to understand how Tau spreads through the brain when encapsulated in exosomes and how this Tau escapes into the cytosol via endolysosomal permeabilization starting corrupting cycles of seeding. Finally, we are using super resolution microscopy to gain insight into the behaviour of Tau and key interacting proteins in the synapse and at the plasma membrane.
In the second part of my talk, I will present our data on using ultrasound to clear Aβ and Tau pathology in AD mouse models and restore memory and motor functions. I will also present data on how ultrasound enhances cognition in physiologically aged mice. On our journey of developing therapeutic ultrasound as a treatment modality for human brain diseases, we have been experimenting in the large animal model sheep (with brain and skull properties similar to those of humans). We have further built a prototype device that will be used in an upcoming safety trial. I will give an overview where we are up to and how we go forward in the coming years.

Professor Jürgen Götz, PhD, is the inaugural Director of the Clem Jones Centre for Ageing Dementia Research at the Queensland Brain Institute in Brisbane (Australia). Professor Götz studied biochemistry in Switzerland and earned his PhD in immunology with Nobel Laureate Köhler in Germany. After postdoctoral work at UCSF and at Novartis, he became a group leader in Zürich, before moving to the University of Sydney in 2005, and then to the University of Brisbane (Queensland Brain Institute) in 2012. A major focus of his laboratory is to gain insight into how tau and amyloid both separately and synergistically contribute to Alzheimer’s disease. In recent years, the laboratory has started to develop therapeutic ultrasound into a treatment modality for Alzheimer’s disease and other brain diseases, both by transiently opening the blood-brain barrier and as a neuromodulatory tool.

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