Proteoglycans/Glycosaminoglycans in the Amyloidotic Lesions of AD

Proteoglycans are a specific group of carbohydrate aolecules that are believed to be present in association with the amyloid “protein” deposits in the brains of Alzheimer’s patients . Although there are several potentially different types of proteoglycans that may be involved, we have been able to identify and localize one type, known as “heparan sulfate proteoglycans”, to the aayloid fibrils in both the neur itic plaques and aayloid deposits in blood vessels (known as congophilic angiopathy) in the brains of Alzheimer’s patients. We have also used specific techniques to retain these proteoglycans in tissues to allow the visualization of these molecules at high magnification, in intimate association with amyloid fibrils in the brains of Alzheimer’s patients .        These same “heparan sulfate proteoglycans” have also been identified and localized to the amyloid plaques in the brains of patients with Downs’s syndrome and in other unrelated types of amyloidosis outside the central nervous system suggesting that “hepar an sulfate proteoglycans” may have a comt10n role in the foraation of aayloid in a host of diseases that involve amyloid deposition.         We have used a variety of aethods to determine if proteoglycans and their carbohydrate constituents (known as glycosaminoglycans) are present in the cerebrospinal fluid and/or blood in both Alzheimer and noraal aged patients. In our initial group of studies we have been successful in isolating glycosaminoglycans froa the cerebrospinal fluid of both normal aged and Alzheiaer patients . This provides the first evidence for the presence of these molecules (glycosaminoglycans) in cerebrospinal fluid. The overall levels of these circulating glycosaminoglycans appear to be decreased in the cerebrospinal fluid of Alzheiaer patients in coaparison to noraal aged controls suggesting that alterations of these molecules are occuring in Alzheimer’s disease. We are now using sophisticated techniques to identify the types of glycosaminoglycans present in the cerebrospinal fluid to determine if the elevation or decrease of a specific class of glycosaainoglycan is reflective of the deposition of glycosaminoglycans in association with amyloid deposits in the brains of Alzheimer patients thereby serving as a potential diagnostic marker for Alzheimer’s disease .