Disassembly of amyloid β-protein fibril by basement membrane components

Abstract

Amyloid β-protein (Aβ) fibril in senile plaque may be related to the pathogenesis of Alzheimer's disease (AD). Basement membrane (BM) components are associated with the plaques in AD brain. It suggests that the BM components may play an important role in the deposition of the plaque. We investigated the potential of BM components, such as type IV collagen (collagen IV) and entactin, to induce disassembly of preformed Aβ1-42 (Aβ42) fibrils in direct comparison to laminin. Thioflavin T assays revealed that these BM components disrupted preformed Aβ42 fibrils in a dose-dependent manner. The high concentration of BM components, 100 μg/mL laminin, 50 μg/mL collagen IV and 50 μg/mL entactin, had most effect on disassembly of preformed Aβ42 fibrils (Molar ratio; Aβ42:laminin = 90:1, Aβ42:collagen IV = 34:1, Aβ42:entactin = 20:1). Circular dichroism spectroscopy data indicated that the high concentration of BM components induced structural transition in Aβ42 from β-sheet to random structures. These results suggest that collagen IV and entactin, as well as laminin, are effective inducers of disassembly of Aβ42 fibrils. The ability of these BM components to induce random structures may be linked to the disassembly of preformed Aβ42 fibrils.