Fig. 8: Altered PSEN2 expression impacts on synapse function and neuronal endolysosomal homeostasis. | Nature Communications

Fig. 8: Altered PSEN2 expression impacts on synapse function and neuronal endolysosomal homeostasis.

From: Altered expression of Presenilin2 impacts endolysosomal homeostasis and synapse function in Alzheimer’s disease-relevant brain circuits

Fig. 8

APPKI mice with altered PSEN2 expression present with increased pathology including plaques and dystrophic neurites. This leads to decreased LTP, specifically within the CA3 region of the hippocampus, impacting working memory. In vivo, mossy fiber synapses are reduced in size and display altered numbers of synaptic vesicles (only the APPxFADPSEN2 is displayed, showing reduced synaptic vesicle densities). In primary hippocampal neurons of APPxPSEN2KO and APPxFADPSEN2, surface expression of GLUA1 and vGLUT1 is strongly lowered compared to APPKI, implying endosomal recycling defects. In these neurons, accumulation of enlarged LE/Lys, autophagosome and autolysosomes can be observed. LE/Lys have reduced basal Ca2+ and Ca2+ release upon stimulation of the TRPML-1, and accumulate APP metabolites, including APP-CTF and Aβ. Created in BioRender. Vrancx, C. (2024) https://BioRender.com/s99m518.

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