Extended Data Fig. 3: Neuron-specific origin of PANTHOS and age/sex dependent PANTHOS neuron proliferation in brains of 5xFAD/TRGL mice.
a. PANTHOS neurons were immunolabeled with neuron specific enolase (NSE) which detects neuronal populations, especially cell bodies, and were counter-stained with DAPI. NSE IHC indicates that PANTHOS neurons were NSE-positive. The UV channel did not produce any autofluorescence from PANTHOS neurons when DAPI counterstaining was not done in 2.7-month-old 5xFAD/TRGL mouse brain. Scale bar 20 μm. b. PANTHOS neurons were immunolabeled with lysosome marker CTSB and LIMP2 in 2.7-month-old 5xFAD/TRGL mouse brain. Scale bar 20 μm. c. tfLC3 signal in cerebral cortex at three ages in 5xFAD/TRGL male and female mice demonstrating age- and sex- dependent proliferation of PANTHOS neurons. d. Overview of PANTHOS neuron distribution in cerebral cortex of the 2.7-month-old 5xFAD/TRGL male mouse (top panel) and dual channel higher magnification (bottom). Scale bar 50 μm. e. Age dependent increased prevalence of the PANTHOS profiles in various AD mouse models. 5xFAD/TRGL: 1.6 mo (0±0), 2.7 mo (2340±33.8), 6 mo (767±62.3); Tg2576/TRGL: 5 mo (0±0), 9 mo (7.0±2.1), 12.6 mo (24.3±3.2); APP51/TRGL: 13 mo (0±0), 20 mo (3.0±0.4), 25-26 mo (48.3±12.2). Data points indicate mouse numbers; mo. denotes age in months. Quantitative data are presented as means ±S.E.M. unpaired t-test, two-tailed P value as indicated. a-d: Experiment was repeated 3 times independently with similar results.
