We previously showed that the nuclear speckle protein MSUT2 and its binding partner PABPN1 reciprocally influence vulnerability to tauopathy, and both become depleted in more severe AD cases [19]. To assess the interaction between cytoplasmic accumulation of pSRRM2 and MSUT2 in AD, we immunostained the frontal cortex of our AD cohort for MSUT2 (Table 3). All AD cases with predominately nuclear pSRRM2 (n = 9) had intact MSUT2 protein levels and milder tauopathy. In contrast, of our 18 AD cases with substantial pSRRM2 cytoplasmic accumulation in the frontal cortex, 14 (78%) had depleted MSUT2 and 17 (94%) exhibited robust or moderate phospho-tau pathology. These data support the idea that MSUT2 depletion contributes to pSRRM2/Tau + co-pathology in AD and suggest nuclear speckle disruption occurs as a cellular feature of AD.Table 3Case IHC data summaryCase #DxpSRRM2MSUT2AT18010ADCytoplasmicDepleted+++6ADCytoplasmicDepleted+++8ADCytoplasmicDepleted+++9ADCytoplasmicDepleted+++16ADCytoplasmicPositive+++5ADCytoplasmicDepleted+++1ADCytoplasmicDepleted+++2ADCytoplasmicDepleted+++3ADCytoplasmicDepleted+++7ADCytoplasmicDepleted++13ADCytoplasmicPositive++11ADCytoplasmicDepleted++4ADCytoplasmicDepleted++12ADCytoplasmicPositive++18ADMixedDepleted+++17ADMixedDepleted+++20ADMixedPositive++19ADMixedDepleted+28ADNuclearPositive++23ADNuclearPositive++29ADNuclearPositive+24ADNuclearPositive+22ADNuclearPositive+21ADNuclearPositive+26ADNuclearPositive+27ADNuclearPositive++, mild; ++, moderate; +++, robust AT180 p-tau accumulation
