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Spatial transcriptomics reveals an unexpected impact of tau and tau pathology on the expression of transthyretin
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DOI：10.3389/fnagi.2025.1656850.png)
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Abstract
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IntroductionRNA 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.MethodsSpatial 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.ResultsWe 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.ConclusionAs 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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