Gangliosides determine the amyloid pathology of Alzheimer's disease

Gangliosides, GM3 and GM1, are suggested to accelerate the deposition of the amyloid beta-protein as amyloid angiopathy and senile plaques, respectively, in the Alzheimer brain. We investigated the profile of amyloid deposition in the brains of transgenic mice expressing a mutant amyloid precursor protein with a disrupted GM2 synthase gene, in which GM3 accumulates whereas GM1 is lacking. These mice showed a significantly increased level of deposited amyloid beta-protein in the vascular tissues. Furthermore, formation of severe dyshoric-form amyloid angiopathy, in which amyloid extended from the blood vessel walls deeply into the surrounding parenchyma was observed. Our results indicate that the expression of gangliosides is a critical determinant for the amyloid pathology in the Alzheimer brain.