|Embalming Amyloid-β: The Role for Aldehyde Stress in Alzheimer's Disease
Zhang and colleagues present novel findings demonstrating that cholesterol derivative-aldehydes resulting from ozonolysis can accelerate the aggregation of Aβ into fibers. This finding importantly extends earlier work showing that aldehydes from lipid peroxidation (Sayre et al., 1997; Takeda et al., 2000; Gómez-Ramos et al., 2003; Pocernich and Butterfield, 2003; Woltjer et al., 2003) and glycation (Smith et al., 1994) play a pivotal role in the genesis of AD pathology.
Oxidative damage to lipids results in the production of several reactive aldehydes that can attack and modify DNA (Marnett, 2002; Luczaj and Skrzydlewska, 2003), proteins (Wataya et al., 2002; Zhang et al., 2003), lipids, and sugars (Woltjer et al., 2003). Aldehyde modifications may contribute to changes of biomolecule properties in two distinct ways: 1) render biomolecules more hydrophobic and 2) potentiate protein crosslinks. These alterations predispose to the occurrence of protein misfolding processes that accumulate...