An Early Olfactory Transcriptomic Signature of Tauopathy

Olfactory dysfunction is an early feature of neurogenerative diseases. PS19 mice, a well-established tauopathy model, show hallmark tau pathology in various regions of the olfactory system. We performed transcriptomic analyses of PS19 mice at 3, 6, and 9 months in the olfactory epithelium (OE), olfactory bulb (OB), and hippocampus to investigate molecular changes linked to tau pathology. Due to the peripheral location and anatomical accessibility of the OE, we also aimed to identify potential early biomarkers of tauopathy. Our analysis revealed region- and age-specific gene expression changes in PS19 mice, with a temporal progression of molecular alterations linked to tau pathology. Among the differentially expressed genes, Gbp2b showed early and consistent upregulation in the OE, highlighting it as a promising early biomarker candidate. The accessibility of the OE makes it a promising site for early tauopathy biomarker discovery. The early expression of Gbp2b suggests potential clinical relevance, warranting validation in human samples.