The role of the Maillard reaction in other pathologies: Alzheimer's disease

Many approaches have and are being undertaken to treat Alzheimer's disease but, as yet, no therapy is available with any established efficacy. Given the heterogeneity of the aetiological factors involved in Alzheimer's disease and the difficulties encountered in the clinical diagnosis, the lack of pharmacological success is not surprising. Furthermore, the lack of an adequate animal model of Alzheimer's disease has delayed the development of novel therapeutic strategies. At present, and with the exception of the rarer forms of familial Alzheimer's disease, the need remains to treat the symptoms rather than the causes of the disease, primarily because the pathogenesis of Alzheimer's disease is still unknown. The evidence for the role of glycation and advanced glycation end-products (AGEs) in the formation of neurofibrillary tangles and neuritic plaques, the characteristic histopathological lesions of Alzheimer's disease, is briefly reviewed. While the role of glycation in the pathogenesis of Alzheimer's disease is not yet unequivocally proven, it is the only single protein modification that would explain the formation of both the characteristic histopathological lesions first described by Alois Alzheimer in 1907. With our improved understanding of the molecular basis for the clinical symptoms of dementia, it is hoped that the aetiological causes will afford more suitable targets for therapeutic intervention. In this respect it is interesting to note that the anti-inflammatory compounds indomethacin and acetylsalicylic acid, both inhibitors of the Maillard reaction, have been reported to have therapeutic potential and the nootropic agent tenilsetam inhibits protein cross-linking by AGEs.