Current Research and Scholarly Interests
I have developed a model of aging in the Brown Norway/Fisher rat and a separate model of chronic hydrocephalus in a kaolin-induced hydrocephalus rat model. We are studying the accumulation of amyloid by immunostaining and ELISA in relation to age and hydrocephalus-induced decrease in CSF formation and turnover, measured by ventricular cisternal perfusion, and the change in expression of the blood-brain barrier receptors for A-beta transport, LRP-1 and RAGE, measured by immunostaining, PCR and western blot.
Thus far we have found that A-beta accumulation increases with age and this increase is related to a decrese in microvessel expression of LRP-1, the endothelial receptor that transports A-beta from the brain to the plasma pool, an increase in microvesselRAGE, the endothelial receptor that transfers A-beta from the plasma to the brain interstitium. CSF production and turnover falls and further A-beta accumulation occurs. Changes similar to advanced aging occur with the rat kaolin-hydrocephalus model, but at an earlier age, and amyloid accumulates prematurely, as is seen in patients with NPH.