Extended Data Fig. 7: PANTHOS neurons evolve into Thio-S positive dense-cored senile plaques in the 5xFAD/TRGL AD mouse model.

a. PANTHOS neurons are not positive for the anti-active caspase-3 antibody in 2.7-month-old, male 5xFAD/TRGL mouse brain. Although active caspase-3 positive cells were extremely rare and did not overlap with PANTHOS, the arrowhead identifies a rare non-neuronal caspase-3-positive cell as a positive control. b. Representative image of PANTHOS with GFP/RFP filter set (left) and image of the additional Thio-S staining with GFP/RFP/DAPI filter in 6-month-old, male 5xFAD/TRGL mouse brain. eGFP signal of the PANTHOS was diminished, whereas mRFP signals were preserved in Thio-S-stained tissues (right) compared to unstained tissue (left). Arrow used as tissue orientation. c. Digital overlay of the ROI (Fig. b, box) highlights that PANTHOS profiles are only detectable using mRFP signal since fixation for Thio-S quenches GFP. A small percentage of PANTHOS were Thio-S negative (arrowhead) whereas the majority are Thio-S positive (arrow) in the cortex of 6-month-old, male 5xFAD/TRGL mouse brain. a-c: Experiment was repeated 3 times independently with similar results.