[47]. Investigation of a small number of human tauopathy cases demonstrated mislocalization of SRRM2 in AD, but did not document the presence of nuclear tau/RNA assemblies [7]. Here, we confirm nuclear clearance and cytoplasmic accumulation of pSRRM2 in a larger AD cohort, and demonstrate variability in pSRRM2 related pathologic changes in the frontal cortex of AD cases. In sum, these studies highlight the dysfunction of nuclear speckles in AD. To further understand the mechanistic disease relevance of nuclear speckle disruption in AD, transcriptomic and proteomic characterization of pSRRM2 + cytoplasmic deposits in AD should be prioritized in future work, and comparison of SRRM2 + deposits between AD brain and model systems may be critical to understand possible disease mechanisms.
