Mechanisms of pathogenesis in the tauopathies
Thursday, July 23, 2020
15:00 UTC
Prof Karen Duff
UK Dementia Research Institute at UCL
Recording
Open recording
Hosted by SONA70 minutes
Abstract
The distribution of pathological tau in the brain of patients with AD is highly predicable, and as 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. Aging 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.
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