Involvement of Complex Carbohydrate Chemistry in Alzheimer’s Disease

The cardinal feature of Alzheimer disease is the extracellular deposition of proteinaceous amyloid-β fibrils as senile plaques. Amyloid-β plays an essential role in disease diagnosis and is also thought by many to be a key mediator of disease pathogenesis. As such, there are tremendous efforts underway to understand mechanisms of amyloid deposition. In this context, it is notable that the actual term amyloid, represents a historical misnomer (being derived from amylose, i.e., starch) and since this realization, the contribution of carbohydrates in disease pathogenesis has largely been ignored. However, recently, two emerging lines of evidence indicate not only that the interaction of carbohydrates with amyloid is a key event in disease pathogenesis but also that therapeutic efforts targeted towards such pathways may prove therapeutically efficacious. First, just over a decade ago, we and others discovered that oxidative glycation, similar if not identical to that found in diabetes, was an early and chronic contributor to the disease. Second, we very recently found evidence for the presence of chitin-like polysaccharides in association with amyloid deposits in the diseased brain. Both carbohydrate-associated changes likely contribute to the physiochemical properties of amyloid (and other disease-related proteins such as tau) and, as such, to the insolubility and protease-resistance of amyloid. In fact, taken together, the findings indicate an emerging and important role for carbohydrates in the pathogenesis of Alzheimer disease.