Development of new screening system for Alzheimer disease, in vitro Aβ sink assay, to identify the dissociation of soluble Aβ from fibrils

Abstract

Aβ is one of the primary therapeutic targets for Alzheimer disease (AD). Aβ vaccination induces the disappearance of Aβ deposits. Since few reports have focused on the reverse phase of Aβ aggregation, we established a new screening system, the in vitro Aβ sink assay, to clarify the process of dissociation of soluble forms from fibrils. Aβ42 was more resistant to dissociation from fibrils to monomers and/or low molecular weight (LMW) soluble oligomers than Aβ40. We applied this system to find a potential therapy for AD. Ultrasound irradiation significantly enhanced the dissociation of soluble Aβ from fibrils, while ultrasound experiments also confirmed the difference between Aβ40 and Aβ42. We found that some compounds enhanced the dissociation of Aβ from fibrils. Here, we proposed that Aβ42 was more resistant to dissociation from fibrils to monomers and/or LMW soluble oligomers than Aβ40, and this system might be useful to identify dissociation of soluble Aβ from fibrils.

Keywords

• Amyloid
• Alzheimer disease
• Memory
• Ultrasound
• Aβ