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Mechanisms of pathogenesis in the tauopathies
Summary:
The distribution of pathological tau in the brain of patients with AD is highly predictable, and as the disease worsens, it spreads transynaptically from initial regions of vulnerability. The reason why only some neurons are vulnerable to the accumulation and propagation of pathological forms of tau and the mechanisms by which tauopathy spreads through the brain are not well understood. Using a combination of immunohistochemistry and computational analysis we have examined pathway differences between vulnerable and resistant neurons. How tau spreads across a synapse has been examined in vitro using different model systems. Our data show that dysregulation of tau homeostasis determines the cellular and regional vulnerability of specific neurons to tau pathology (H. Fu et al. 2019. Nat. Neuro. 22 (1):47-56) and that deficits in tau homeostasis can exacerbate tau accumulation and propagation. Ageing appears to impact similar neuronal populations. Mechanisms and consequences of abnormal tau accumulation within neurons, its transfer between cells, pathology propagation and therapeutic opportunities will be discussed.

Jul 23, 2020 04:00 PM in London

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Speakers

Karen Duff
Professor @UK Dementia Research Institute at UCL
Prof. Duff has worked on AD and the tauopathies for more than 25 years and received the Potamkin Prize for this work in 2006. She has a strong interest in neurodegenerative disease aetiology and has created various mouse models for AD, tauopathy and synucleinopathy, which have facilitated the study of many aspects of pathogenesis. She uses a broad range of human-relevant experimental approaches (in vitro and in vivo models, multi-omics and computational approaches, in vivo imaging, cognitive tests) to explore pathogenic mechanisms and to identify novel targets and therapeutic approaches.