Figure 1:

Oligomeric Aβ(1–42)-induces lipid peroxidation. Oligomeric Aβ(1–42) embedded in the lipid bilayer initiates free radical formation (R^.) mediated by Met 35 which leads to abstraction of a labile, allylic hydrogen atom from unsaturated fatty acids forming lipid radicals (L^.) that rapidly combine with oxygen to form lipid peroxyl radicals (LOO^.). Lipid peroxyl radicals propagate lipid peroxidation by abstracting allylic hydrogen atoms from other unsaturated fatty acids in the membrane forming lipid hydroperoxides (LOOH) and lipid radicals (L^.), thereby propagating the chain reaction. The reactive lipid peroxidation product, 4-hydroxy-2-trans-nonenal (HNE) can be formed from lipid hydroperoxides of arachidonic acid, linoleic acid, and linolenic acid. This process of lipid peroxidation, coupled to HNE formation and subsequent reaction with and dysfunction of cellular proteins, amplifies greatly the effects of a small amount of free radical formation on Aβ(1–42).