Fig. 1

Derangement of nuclear speckle marker pSRRM2 (ab SC-35) in AD. Immunohistochemistry using a pSRRM2 recognizing antibody raised against purified human spliceosomes (clone SC-35, see Table 2). Human pSRRM2 stains nuclear speckles within neurons in the frontal cortex of the normal adult human brain (a). A subset of AD donors (30%) also exhibit normal nuclear speckle staining in cortical neurons (b), however, the majority of AD donors (72%) exhibit striking mis-localization of pSRRM2 to the cytoplasm in neurons in the frontal cortex (c). Additionally, all AD donors exhibited mis-localization of pSRRM2 in the hippocampus (d) and amygdala (e), brain regions where tauopathy occurs earlier in disease progression. AD donors with aberrant cytoplasmic pSRRM2 in tauopathy rich regions showed normal nuclear pSRRM2 distribution in cerebellar neurons (f), which do not typically exhibit any tau pathology. Scale bars, 50 µm