Journal of Alzheimers Disease & Parkinsonism
Open Access

Garth F Hall

Biography

Research Interest

My current research focuses on the integration of tau pathobiology at the cellular level with intercellular aspects of tauopathy pathogenesis. Since tau is universally known as an exclusively intracellular protein which is never secreted to the extracellular space, it has been assumed until very recently that tau protein cannot be secreted and thus can only reach the CSF once the neurons that synthesized it have died. We recently showed that tau protein is secreted by viable neurons in both cell culture and in situ (i.e. lamprey ABC) models of AD without the aid of anti-aggregation agents such as NNI328, and that tau secretion requires the N terminus28 and is significantly inhibited by the presence of the N terminal exon 2 sequence29, confirming that tau release is due to an active biological process. This work challenged the assumption that tau release must be passive and was initially difficult to publish. However, our findings together with congruent findings in other systems-(i.e. that tau can be taken up into adjacent neurons in culture30 and can be transferred between neurons in a mouse model31) have kindled interest in interneuronal tau movement in the AD/tauopathy research community, since it is now becoming clear that tau secretion may have important ramifications for the development of AD diagnostics and possibly for our overall understanding of the role of tau pathobiology in human disease. We are currently characterizing the tau secretion mechanism in more detail using both lamprey and cell culture models and have begun to extend this work to human brain and CSF samples from AD patients, using the absence of exon 2 secreted tau has a specific biomarker to ask whether tau secretion plays a role in the genesis of elevated CSF-tau in AD32-33.

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