ADVANCED MAILLARD REACTION END-PRODUCTS ARE ASSOCIATED WITH ALZHEIMER-DISEASE PATHOLOGY

During aging long-lived proteins accumulate specific post-translationa l modifications. One family of modifications, termed Maillard reaction products, are initiated by the condensation between amino groups of p roteins and reducing sugars. protein modification by the Maillard reac tion is associated with crosslink formation, decreased protein solubil ity, and increased protease resistance. Here, we present evidence that the characteristic pathological structures associated with Alzheimer disease contain modifications typical of advanced Maillard reaction en d products. Specifically, antibodies against two Maillard end products , pyrraline and pentosidine, immunocytochemically label neurofibrillar y tangles and senile plaques in brain tissue from patients with Alzhei mer disease. In contrast, little or no staining is observed in apparen tly healthy neurons of the same brain. The Maillard-reaction-related m odifications described herein could account for the biochemical and in solubility properties of the lesions of Alzheimer disease through the formation of protein crosslinks.