Effect of aldehydes derived from oxidative deamination and oxidative stress on β-amyloid aggregation;: pathological implications to Alzheimer's disease

Formaldehyde and methylglyoxal are generated via deamination from methylamine and aminoacetone respectively catalyzed by semicarbazide-sensitive amine oxidase (SSAO). Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are end products of lipid peroxidation due to oxidative stress. These aldehydes are capable of inducing protein cross-linkage. Elevated levels of aldehydes were found in Alzheimer's disease (AD). These reactive metabolites may potentially play important roles in beta-amyloid (A beta) aggregation related to the pathology of AD. In the present study thioflavin-T (ThT) fluorometry, an immuno-dot-blot assay and atomic force microscopy (AFM) were employed to reveal the effect of aldehydes on A beta aggregation in vitro. The target on A beta for interaction with formaldehyde was identified. The results support the involvement of endogenous aldehydes in amyloid deposition related to AD.