Accumulation of amyloid β protein in Tg2576 mice

The progressive deposition of amyloid beta protein (Abeta) is a crucial step of Alzheimer's disease (AD). To detect when and where Abeta begins to deposit, we examined fractions by sucrose gradient centrifugation from Tg2576 mouse brains, an animal model of AD. Precursors of Abeta, beta-secretase and putative gamma-secretase were all recovered in lipid rafts, which are low density, detergent-insoluble membrane fractions. The major Abeta catabolizing enzyme, neprilysin, and apolipoprotein E also co-localized in lipid rafts. In 3-month-old Tg2576, about 20% of total Abeta40 and Abeta42 were detected in lipid rafts. From 7-8 months, the early stage of amyloid deposition, Abeta42 increased in lipid rafts. These results suggested that lipid rafts may be crucial sites for Abeta production, Abeta degradation and Abeta aggregation leading to early accumulation of Abeta amyloid. (C) 2003 Elsevier Science B.V. All rights reserved.