Further evidence of local ganglioside-dependent amyloid beta-protein assembly in brain.

We investigated the molecular mechanism underlying the region-specific deposition of amyloid beta-protein in brains affected with Alzheimer's disease or cerebral amyloid angiopathy. Here, we show that a hereditary variant-type ('Iowa') amyloid beta-protein, which predominantly deposits in the cerebral vessel wall similar to Dutch and Italian-type amyloid beta-proteins, preferably assembles in the presence of GM3 ganglioside. On the basis of our previous findings that first, cerebrovascular smooth muscle cells that provide favorable sites for these variant-type amyloid beta-proteins exclusively express GM3 ganglioside, and second, Dutch and Italian-type amyloid beta-proteins also require GM3 ganglioside for their assembly, our results provide further evidence that local gangliosides play a crucial role in the region-specific amyloid beta-protein deposition in the brain.