BRAIN ENDOTHELIAL-CELL ENZYMES CLEAVE PLATELET-RETAINED AMYLOID PRECURSOR PROTEIN

We have previously demonstrated that thrombin-activated platelets from patients with advanced Alzheimer's disease (AD) retain significantly more surface membrane-bound amyloid precursor protein (mAPP) than plat elets from non-demented age-matched individuals (AM). We have studied interactions between these platelets and the cerebrovascular endotheli um to which activated platelets adhere in a model system, investigatin g their involvement in the formation of amyloid beta peptide (A beta) deposits in AD patients, We report here that there appear to be alpha and beta secretase-like activities in primary human blood brain barrie r endothelial cell (BEC) cultures from both AD patients and AM control subjects (AD-BEC and AM-BEC, respectively) as well as a gamma secreta se-like activity that appears only in AD-BEC, No such activities were observed in human umbilical vein endothelial cells (HUVECs). Furthermo re, there is more penetration of the platelet-released products platel et factor 4 and soluble APP through the BEC layer grown from AD patien ts than that grown from AM individuals, whereas none penetrate through a HUVEC layer, Thus the interaction between platelets, the APP they h ave retained or released, and cerebral vascular endothelial cells may be at least partially responsible for amyloidogenic deposits around th e cerebral vasculature of AD patients.