Assembly of hereditary amyloid β-protein variants in the presence of favorable gangliosides

The mechanisms underlying regional amyloid β-protein (Aβ) deposition in brain remain unclear. Here we show that assembly of hereditary variant Dutch- and Italian-type Aβs, and Flemish-type Aβ was accelerated by GM3 ganglioside, and GD3 ganglioside, respectively. Notably, cerebrovascular smooth muscle cells, which compose the cerebral vessel wall at which the Dutch- and Italian-type Aβs deposit, exclusively express GM3 whereas GD3 is upregulated in the co-culture of endothelial cells and astrocytes, which forms the cerebrovascular basement membrane, the site of Flemish-type Aβ deposition. Our results suggest that regional Aβ deposition is induced by the local gangliosides in the brain.