Human brain banks are essential for studying a wide variety of neurological and neurodegenerative diseases, yet the variability in postmortem interval (PMI)-the time from death to tissue preservation-poses significant challenges due to rapid cellular decomposition, protein alterations, and RNA degradation. Furthermore, the postmortem transcriptomic alterations occurring within distinct cell types are poorly understood. In this study, we analyzed the effect of a 3 h postmortem interval on single-nucleus RNA signatures in the brains of wild-type (WT) and PS19 mice, a common model of tauopathy. We observed that basic quality control metrics (such as the number of genes and reads per cell), total nuclei counts, and RNA integrity number (RIN