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 speckles within neuronal nuclei to the soma, with pSRRM2 accumulating in the cytoplasm. This abnormal pSRRM2 staining pattern occurs in the frontal cortex in 20 out of 29 AD cases. Furthermore, this cytoplasmic distribution of pSRRM2 was detected in all 29 AD cases in the hippocampus and amygdala, regions known to accumulate abundant tau pathology at an earlier stage in the disease process. In contrast, we did not observe pSRRM2 mis-localization in the cerebellum, a brain region generally spared from neurodegeneration and pathological tau in AD; rather we observed a normal pattern clearly marking nuclear speckles. Taken together, the pattern of neurons exhibiting pSRRM2 mis-localization parallels the pattern of pathological neurofibrillary tangle deposition in AD brain.Table 2AntibodiesAntigenClone/product nameDilutionHost speciesSourceCatalog #pSRRM2SC-351:200MouseSigmaAldrichS4045pTauThr231AT1801:200MouseThermoScientific (Rockford, IL, USA)MN1040NeuNA601:400mouseMilliporeMAB377Tau (Total)SP70 pAb1:1,000RabbitRockland Immunochemicals Inc. (Limerick, PA, USA)200-C01-B33pTau Ser202CP13 mAb1:500MousePeter Davies (Litwin-Zucker Research Center for the Study of Alzheimer's Disease, The Feinstein Institute of Medical Research, Northwell Health, Manhasset, NY, USA)N/ApTau Ser396/Ser404PHF-1 mAb1:2,000MousepTauSer422EPR2866 mAb1:500RabbitAbcam (Cambridge, UK)ab79415pTau Thr181AT270 mAb1:15,000MouseThermoFisher
