Nov 6, 2018

Ectopic expression induces abnormal somatodendritic distribution of tau in the mouse brain

BioRxiv : the Preprint Server for Biology
Atsuko KuboTomohiro Miyasaka

Abstract

Tau is a microtubule-associated protein that is localized to the axon. In Alzheimer's disease, the distribution of tau undergoes a remarkable alteration, leading to the formation of tau inclusions in the somatodendritic compartment. To investigate how this mis-localization occurs, we recently developed immunohistochemical techniques that can separately detect endogenous mouse and exogenous human tau with high sensitivity, which allows us to visualize not only the pathological but pre-aggregated tau in mouse brain tissues of both sex. In tau transgenic mouse brains, exogenous human tau was abundant in dendrites and somata even in the presymptomatic period, whereas the axonal localization of endogenous mouse tau was unaffected. In stark contrast, exogenous tau was properly localized to the axon in human tau knock-in mice. We tracked this difference to the temporal expression patterns of tau. Tau mRNA was continuously expressed in the transgenic mice, whereas endogenous tau and exogenous tau in the knock-in mice exhibited high expression levels during the neonatal period and strong suppression into the adulthood. These results indicated the uncontrolled expression of exogenous tau beyond the developmental period as a cause of mis-...Continue Reading

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Mentioned in this Paper

Establishment and Maintenance of Localization
Tauopathies
Microtubule-Associated Proteins
Immunohistochemistry
Aggregation
Brain
MAPT protein, human
House mice
Myocardial Infarction
Alzheimer's Disease

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