Identification of Tau protein as a novel marker for maturation and pathological changes of oligodendrocytes

Abstract Microtubule‐associated protein Tau is primarily expressed in axons of neurons, but also in Olig2‐positive oligodendrocytes in adult rodent and monkey brains. In this study, we sought to determine at what cell stage Tau becomes expressed in the oligodendrocyte lineage. We performed immunostaining of adult mouse brain sections using well‐known markers of oligodendrocyte lineage and found that Tau is expressed in mature oligodendrocytes, but not in oligodendrocyte progenitors and immature pre‐oligodendrocytes. We also investigated Tau expression in developing mouse brain. Surprisingly, Tau expression occurred after the peak of myelination and even exceeded GSTπ expression, which has been considered as a marker of myelinating oligodendrocytes. These results suggest Tau as a novel marker of oligodendrocyte maturation. We then investigated whether Tau is important for oligodendrocyte development and/or myelination and how Tau changes in demyelination. First, we found no changes in myelination and oligodendrocyte markers in Tau knockout mice, suggesting that Tau is dispensable. Next, we analyzed the proteolipid protein 1 transgenic model of Pelizaeus‐Merzbacher disease, which is a rare leukodystrophy. In hemizygous transgenic mice, the number of Tau‐positive cells were significantly increased as compared with wild type mice. These cells were also positive for Olig2, CC1, and GSTπ, but not PDGFRα and GPR17. In stark contrast, the expression level of Tau, as well as GSTπ, was dramatically decreased in the cuprizone‐induced model of multiple sclerosis. Taken together, we propose Tau as a new marker of oligodendrocyte lineage and for investigating demyelination lesions.