Utilizing single-nuclei RNAseq analysis (SnRNAseq) on hippocampal tissues to isolate the effects on varied cell types, we uncovered that DAP12 not only plays a role in driving the formation of disease-associated microglia, but also significantly shapes the transcriptomic states of oligodendrocytes, leading to an intermediate state concurrent with brain demyelination in tauopathy. Here, TYROBP is linked to tauopathy.