Our efforts over the past five years to simultaneously image lipid rafts and associated proteins in the neuronal membrane have now been published in iScience. While further advancements in resolution are needed, this approach has allowed us to propose that the increase in APP levels within lipid raft domains may underlie ApoE4 astrocyte-induced neuronal Aβ overproduction. This mechanism is distinct from the clathrin-mediated endocytosis of APP and subsequent endosomal processing observed in neurons carrying the APPswe mutation. Instead, it appears to be clathrin-mediated endocytosis independent and closely linked to cholesterol dysregulation driven by astrocytic ApoE4. Please refer to the paper below for further details.
https://doi.org/10.1016/j.isci.2025.111893
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