Since sut-2 and its homolog MSUT2 enable the development of tau pathology and appear to reside in nuclear speckles within the nuclei of neurons [13, 16, 25], we hypothesized that nuclear speckle function may play an important role in the genesis or progression of pathological tau. To further investigate the involvement of nuclear speckles in neurodegenerative tauopathy, we immunostained brain sections from AD cases for the canonical nuclear speckle marker monoclonal antibody (mAb) clone SC-35. The mAb SC-35 was originally raised against purified human spliceosomes and has recently been conclusively demonstrated to recognize a phosphorylated epitope of human SRRM2 (pSRRM2) protein [24, 26]. SRRM2 protein plays a key role in mRNA splicing as a nuclear matrix protein [27, 28] and is a critical nuclear speckle co-scaffolding protein with SON protein [26]. Immunostaining with mAb SC-35 demonstrates a clear disruption of the normal canonical nuclear speckle staining pattern in the frontal cortex of a majority of AD cases, but not in age-matched controls (Fig. 1). The striking mis-localization of SRRM2 appears to be a relocalization of pSRRM2 protein from the nuclear
