The blood-brain barrier is a poorly permeable interface between central nervous system (CNS) and peripheral circulation vital for homeostasis within the brain parenchyma. It consists of endothelial cells with specialised features including the presence of multidrug transporters of the ATP-Binding cassette (ABC) family, P-glycoprotein (Pgp), MRP4 and BCRP. These play important roles in limiting movement of substances into and enhancing their efflux from the brain. These special features of brain endothelial cells are maintained by signals from the surrounding brain. Such signals may be altered in CNS pathologies such as Alzheimer’s disease (AD) which is characterised by accumulation of beta amyloid aggregates within the brain, particularly around cerebral vessels. Previous studies [1] have reported decreases in the glucose transporter, Glut-1, in the brain vasculature of AD patients. In addition, an inverse correlation has been found between amyloid deposition and Pgp expression [2] in non-demented subjects. The present study investigates the status of multidrug transporters in brain microvasculature of subjects with AD and compares their levels of expression with those found in brain vasculature of normal human subjects. Sections of frozen brain from hippocampal region, middle frontal gyrus and middle temporal gyrus were obtained from 7 subjects with AD and 7 age-matched normal subjects provided by the Neurological Foundation of New Zealand Human Brain Bank under ethical approval. These were subjected to dual fluorescence immunochemical staining using antibodies against Pgp, Glut-1, BCRP or MRP4 and von Willebrand factor. Expression of each protein was assessed using confocal microscopy, quantifying peak fluorescence values of cross sectional profiles across brain microvessels, 8-10 vessels being analysed per section. The conditions for use of each antibody that would permit detection of any expression differences were first established by comparing staining on cell lines that over- or under-express each of the transporters of interest. Results revealed that expression of P-gp was significantly reduced in brain microvessels in hippocampal regions of patients with AD compared to normal individuals (p=0.005). Decreases in Glut-1 were also evident on the microvessels in these same regions (p<0.001). Decreases seen in expression of MRP4 or BCRP did not reach significance. The mechanisms responsible for the altered Pgp expression are not yet known but one possible pathway shown to influence Pgp transcription [3] and known to be altered in AD [4] is that involving Wnt/beta catenin. Involvement of this pathway in the alterations seen to blood-brain barrier characteristics in AD is now being explored.