To test the hypothesis that pSRRM2 + lesions overlap with pathological tau, we conducted co-immunofluorescent staining with antibodies against tau and pSRRM2 to fluorescently label pSRRM2 + and Tau + deposits in AD cases. From our co-labeling studies, we observe no obvious co-localization between SC-35 staining of pSRRM2 and pTau in cognitively normal controls (Fig. 3a). However, we observe strong co-localization between pSRRM2 and pTau in AD cases, with Pearson coefficient of colocalization (PCC) of 0.99 (Fig. 3b). In addition, pSRRM2 becomes depleted from the nucleus in cases with cytoplasmic pSRRM + deposits both in tangle bearing and non-tangle bearing neurons. Further we demonstrated by proximity ligation assay that the tau positive lesions remain in close proximity to pSRRM2 + lesions localized in the cytoplasm of cortical neurons predominantly in AD patient brains but not age matched control brains (Fig. 3c).
