Chemical-Driven Outflow of Dissociated Amyloid Burden from Brain to Blood.

Abstract

Amyloid-β (Aβ) deposition in the brain is a primary biomarker of Alzheimer's disease (AD) and Aβ measurement for AD diagnosis mostly depends on brain imaging and cerebrospinal fluid analyses. Blood Aβ can become a reliable surrogate biomarker if issues of low concentration for conventional laboratory instruments and uncertain correlation with brain Aβ are solved. Here, brain-to-blood efflux of Aβ is stimulated in AD transgenic mice by orally administrating a chemical that dissociates amyloid plaques and observing the subsequent increase of blood Aβ concentration. 5XFAD transgenic and wild-type mice of varying ages and genders are prepared, and blood samples of each mouse are collected six times for 12 weeks; three weeks of no treatment and additional nine weeks of daily oral administration, ad libitum, of Aβ plaque-dissociating chemical agent. By the dissociation of Aβ aggregates, the altered levels of plasma Aβ distinguish between transgenic and wild-type mice, displaying potential as an amyloid burden marker of AD brains.