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Chunk #6 — Materials and methods — Brain tissue from AD and control cases

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Pathological tau drives ectopic nuclear speckle scaffold protein SRRM2 accumulation in neuron cytoplasm in Alzheimer's disease.
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Samples of postmortem brain tissue were obtained from the University of Washington (UW) Alzheimer’s Disease Research Center (ADRC) and the Adult Changes in Thought (ACT) Study via the UW BioRepository and Integrated Neuropathology Laboratory. Informed consent for research brain donation was obtained from the legal next of kin according to protocols approved by the UW Institutional Review Board. AD cases (n = 29) were selected based on a clinical diagnosis of dementia and autopsy-confirmed AD neuropathologic change (ADNC) sufficient to explain dementia. Control postmortem brain samples (n = 7) were from age-matched cognitively normal research participants with autopsy-confirmed absent-low levels of ADNC. Donor brains were fixed in 10% neutral buffered formalin for at least two weeks, coronally sliced, and samples of prefrontal cortex, hippocampus, amygdala and cerebellum processed and embedded in paraffin, and sectioned at 5 micron thickness according to routine protocols. Tissue was subjected to histological and neuropathological analysis as described below (Table 1).Table 1Case detailsCase #Dx (NP verifiedAge at deathSexAge at onsetDuration (years)PMI (hrs)NIA-AA B scoreNIA-AA C score1AD76M65114:30332AD82F55278:00333AD60F5467:30224AD82M7668:00235AD80F69116:00336AD71F60115:00337AD81F71104:00338AD70F6285:00339AD68M58109:253310AD77M57207:253311AD84F7684:473312AD93F8496:303113AD62M5574:323314AD88F77115:403315AD78M7267:003316AD86F76108:323317AD75M64114:303318AD90F76146:233319AD89F8275:233220AD77M7166:323321AD78F6992:203222AD94M9133:053323AD86M8062:403324AD77M63145:202325AD100F82183:083226AD91M8297:003227AD94M82124:253328AD86M8154:253329AD89M8636:253330CNT92MNANA4:201131CNT81MNANA5:451132CNT78FNANA6:001133CNT95MNANA4:001134CNT91FNANA6:002135CNT78MNANA5:352136CNT79FNANA7:0011