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

Abstract
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.