COMPOSITIONS AND METHODS FOR ADVANCED GLYCOSYLATION ENDPRODUCT-MEDIATED MODULATION OF AMYLOIDOSIS

摘要

The present invention relates generally to the non-enzymatic glycosylation of amyloidogenic proteins and the consequent formation of advanced glycosylation endproducts (AGEs). It has been found that formation of AGE-amyloidogenic proteins can enhance amyloidosis. The invention further relates to compositions and methods for the prevention and treatment of amyloidosis associated with amyloid diseses, particularly neurodegenerative disese and Type II diabetes, and more particularly Alzheimer's disese. In a specific example, aggregation of an amyloidogenic peptide, .beta.AP, is enhanced by the glycosylation reaction of .beta.AP to form AGE-.beta.AP as defined herein. Accordingly, the invention extends to a method for modulating the in vivo aggregation of amyloid polypeptides and associated amyloidosis by controlling the formation and presence of AGE-amyloid polypeptide. A corresponding diagnostic utility comprises the measurement of the course and extent of amyloidosis by a measurement of the presence and amount of AGEs and particularly, AGE-amyloid. An assay is included that may use the AGE-amyloid polypeptide of the present invention to identify disease states characterized by the presence of AGE-amyloid. Additionally, such an assay can be utilized to monitor therapy and thus adjust a dosage regimen for a given disese state characterized by the presence of AGE-amyloid.