Publisher Summary Protein modification, aggregation, and deposition feature prominently in many pathological processes and can play a direct, etiological role in tissue damage. The amyloidoses, for example, are characterized by the aggregation and progressive insolubilization of proteins or their fragments, leading to an accumulation of deposits that are resistant to proteolytic removal and normal tissue remodeling. The intra- and extracellular aggregates that comprise the senile plaques, the neurofibrillary tangles, and the amyloid deposits of the cerebrovasculature are considered the pathological hallmarks of Alzheimer's dementia, a degenerative disease of the central nervous system. Similarly, amyloid deposition within the pancreatic islets of Langerhans occurs as a result of the aggregation and insolubilization of islet amyloid polypeptide (IAPP) and is associated with progressive r-cell dysfunction and the development of type II diabetes mellitus. Amyloid-containing deposits also occur in the systemic amyloidoses associated with hemodialysis, chronic inflammation, cancer, and aging. Other forms of protein aggregation have also been described in association with degenerative conditions such as neurofilament conglomeration in amyotrophic lateral sclerosis. This chapter describes the present state of methodology for the detection of advanced glycation end-products (AGEs). While no single method may prove suitable for a particular experimental system or tissue-derived substance, the combination of immunochemical, high-performance liquid chromatography (HPLC), and mass spectroscopic methods has proven to be a powerful approach for the detection and quantitation of glycation-type covalent modifications in a variety of in vitro and in vivo settings. This chapter also discusses the experimental application of a new class of pharmacological agents capable of chemically dissociating AGE cross-links and physically “breaking” the covalent bond linking two polypeptide chains.
