Accumulation of amyloid β protein in Tg2576 mice

The progressive deposition of amyloid β protein (Aβ) is a crucial step of Alzheimer's disease (AD). To detect when and where Aβ begins to deposit, we examined fractions by sucrose gradient centrifugation from Tg2576 mouse brains, an animal model of AD. Precursors of Aβ, β-secretase and putative γ-secretase were all recovered in lipid rafts, which are low density, detergent-insoluble membrane fractions. The major Aβ catabolizing enzyme, neprilysin, and apolipoprotein E also co-localized in lipid rafts. In 3-month-old Tg2576, about 20% of total Aβ40 and Aβ42 were detected in lipid rafts. From 7–8 months, the early stage of amyloid deposition, Aβ42 increased in lipid rafts. These results suggested that lipid rafts may be crucial sites for Aβ production, Aβ degradation and Aβ aggregation leading to early accumulation of Aβ amyloid.