Fig. 8: Time lapse imaging of a single neuron elucidates pathological cascade. | Nature Communications

Fig. 8: Time lapse imaging of a single neuron elucidates pathological cascade.

From: YAP-dependent necrosis occurs in early stages of Alzheimer’s disease and regulates mouse model pathology

Fig. 8

a Time lapse imaging protocol of a single neuron to analyze relationship between intracellular localization of YAP, intracellular Aβ and ER ballooning. Representative images of the same cells (similar to the cells in b) are shown in right panels. b Time lapse imaging of an iPSC-derived neurons carrying APP mutations (homozygous mutants carrying APP KM670/671NL). Nuclear YAP was shifted to intracellular Aβ in the cytoplasm (magenta arrow) and further to ballooned ER (green arrow). YAP was released to extracellular space via leakage of ballooned ER (white arrow) while intracellular Aβ remains as aggregates (blue arrow). The details were described in the text. c Chronological change of nuclear YAPdeltaC intensity and cytoplasmic BTA intensity in three iPSC-derived neurons carrying APP mutations. d Immunohistochemistry of human cerebral cortex with anti-calnexin, an ER membrane marker, and anti-YAP antibodies. Abnormal localizations of YAP in the cytoplasm or ballooned ER were observed frequently observed in MCI patients and at a low frequency in AD patients (white arrow), consistently with the findings in iPSC-derived neurons carrying APP mutations. Source data are provided as a “Source Data file”.

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