Extended Data Fig. 5: High resolution EM images of Fig. 5 panels reveal the contribution of AL fusion with a tubular central perinuclear network of strong Aβ/APP-βCTF IR. | Nature Neuroscience

Extended Data Fig. 5: High resolution EM images of Fig. 5 panels reveal the contribution of AL fusion with a tubular central perinuclear network of strong Aβ/APP-βCTF IR.

From: Faulty autolysosome acidification in Alzheimer’s disease mouse models induces autophagic build-up of Aβ in neurons, yielding senile plaques

Extended Data Fig. 5

a. Enlarged EM image of Fig. 5c-ii. AVs indicated with yellow arrowheads in continuity with a membranous tubular network containing fibrous bundles (red arrowheads). Scale bar 1 μm. b. Full resolution image of Fig. 5d revealing continuity of AVs (yellow arrowheads) and the tubular network (light-blue arrowheads) in greater detail. Scale bar 500 nm. c. IHF labeling with antibodies to the neuronal cytoskeleton protein NFL and lysosomes (CTSB, LAMP2) in 2.7-month-old 5xFAD/TRGL mouse brain. NFL positive swollen process projecting peripherally from the PANTHOS neuron contrasts with the perikaryal blebs which have undetectable NFL signal consistent with the NFL process being a dystrophic axon (arrow). Scale bar 20 μm. d. IHF labeling with neuronal cytoskeleton protein NFL in 6-month-old 5xFAD/TRGL mouse brain. NFL positive swollen DN-like profiles are characteristically located at the periphery of the PANTHOS neuron. Scale bar 20 μm. e. IEM detection of strong immunolabeling for the nuclear marker (KDMA/LSD1 - blue arrows in box inset) in the area of a nucleus no longer identifiable morphologically in a PANTHOS neuron. Scale bar 5 μm and 1 μm (enlarged ROI). a-e: Experiment was repeated 3 times independently with similar results.

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