Figure 1. Aged‐related changes in cholesterol and gangliosides in the neuronal plasma membrane .

A, in young adult human and rodent neurons, approximately 85% of plasmalemmal cholesterol is found within the cytofacial leaflet while the majority of glycosphingolipids (e.g. GM1 gangliosides) are found in the exofacial leaflet. Both gangliosides and cholesterol enhance the negative curvature property of the plasma membrane, thus enhancing the fusogenicity with presynaptic vesicles (PSV). B, however, with age there is either a reduction in membrane gangliosides and cholesterol or a redistribution of cholesterol from the cyto‐ to the exofacial leaflet. These age‐related changes in cholesterol membrane content and distribution drastically impede PSV docking and fusion with the cytofacial leaflet, neurotransmitter release and postsynaptic signalling (e.g. NMDAR and AMPAR), synaptic plasticity (i.e. LTP) and strength, and behaviour.