GM1 ganglioside regulates the proteolysis of amyloid precursor protein

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Abstract
Plaques containing amyloid β-peptides (Aβ) are a major feature in Alzheimer's disease (AD), and GM1 ganglioside is an important component of cellular plasma membranes and especially enriched in lipid raft. GM1-bound Aβ (GM1/Aβ), found in brains exhibiting early pathological changes of AD including diffuse plaques, has been suggested to be involved in the initiation of amyloid fibril formation in vivo by acting as a seed. However, the role of GM1 in amyloid β-protein precursor (APP) processing is not yet defined. In this study, we report that exogenous GM1 ganglioside promotes Aβ biogenesis and decreases sAPPα secretion in SH-SY5Y and COS7 cells stably transfected with human APP695 cDNA without affecting full-length APP and the sAPPβ levels. We also observe that GM1 increases extracellular levels of Aβ in primary cultures of mixed rat cortical neurons transiently transfected with human APP695 cDNA. These findings suggest a regulatory role for GM1 in APP processing pathways.