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Updated: Jul 2, 2026
An In Vitro Model for Studying Tau Aggregation Using Lentiviral-mediated Transduction of Human Neurons
Published on: May 23, 2019
Spatial transcriptomics reveals an unexpected impact of tau and tau pathology on the expression of transthyretin
Deborah L Croteau1,2, Jose Fernandez Navarro3, Thomas Comptdaer4
1National Institute on Aging, Section on DNA Repair, Baltimore, MD, United States.
Introduction:
RNA expression is modulated by tau. We used two mouse models, THY-Tau22 mice, which express pro-aggregation tau, and TauKO mice, which are null for tau, to improve our understanding of tau-altered mRNA expression in brain.
Methods:
Spatial transcriptomics on Tau22 and TauKO mice were used to interrogate regional mRNA expression changes. We focused on mRNA expression changes in the hippocampus and ventricles; two regions altered early in Alzheimer's disease.
Results:
We identified the transthyretin mRNA, Ttr, as being dysregulated in a tau-dependent manner. Immunofluorescence (IF) revealed increased TTR protein expression in THY-Tau22 mice and lowered expression in TauKO mice in the choroid plexus epithelial cells.
Conclusion:
As TTR is involved in the clearance of Aβ and the prevention of Aβ aggregation, we evaluated endogenous mouse Aβ in TauKO mice and observed increased Aβ deposits. Our study reveals a hitherto unknown regulatory role of tau on Ttr mRNA and protein expression, which may participate in a feedback loop contributing to Aβ disease progression.
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