Fig. 4

pSRRM2 mis-localization in AD associates with disease severity. Cytoplasmic pSRRM2 accumulation in AD brain is associated with a more aggressive disease progression. a AD donors with predominately cytoplasmic pSRRM2 in postmortem frontal cortex (n = 20) had an earlier age of disease onset compared to those with primarily nuclear pSRRM2 distribution (n = 9) (**p = 0.0042 by two-tailed Student’s t test). b Representative brain sections from frontal cortex of an AD donor with normal nuclear pSRRM2 distribution (top) compared to an AD donor with abnormal cytoplasmic accumulation of pSRRM2 (bottom) stained with the anti-phosphorylated tau antibody AT180. Brain tissue from cases with cytoplasmic pSRRM2 exhibited more pathological tau. Densitometry analysis of AT180-positive reactivity in AD cases with nuclear (n = 8) or cytoplasmic (n = 19) pSRRM2 (***p = 0.0002 by two-tailed Student’s t test). c Representative brain sections from postmortem brain frontal cortex of an AD donor with normal nuclear pSRRM2 distribution (top) compared to an AD donor with abnormal cytoplasmic accumulation of pSRRM2 (bottom) stained with the neuronal marker NeuN. Brain tissue from cases with cytoplasmic pSRRM2 exhibited decreased NeuN immunoreactivity (indicative of more neuronal loss). Densitometry analysis of NeuN-positive reactivity in AD cases with nuclear (n = 9) or cytoplasmic (n = 18) pSRRM2 (**p = 0.0025 by two-tailed Student’s t test). Scale bars, 250 µm