Permeability of the blood-brain barrier to albumin and insulin in the young and aged SAMP8 mouse

The decrease in the insulin cerebrospinal fluid/serum ratio seen in Alzheim er's disease has been suggested as a mechanism by which brain glucose utili zation could be perturbed. Insulin is transported across the blood-brain ba rrier (BBB) by a system that is altered by pathophysiological events. We us ed SAMP8 mice, a strain that by 8-12 months of age develops severe deficits in learning and memory, to determine whether the insulin transporter or BB B integrity was altered with aging. BBB integrity was measured by injecting radioactive albumin intravenously, washing out the vascular space up to 17 hours later, and measuring brain/serum ratios. This very sensitive method found no increase in the permeability of the BBB to albumin in young and ag ed SAMP8 mice. This compares with previous studies in humans with Alzheimer 's disease and in other colonies of SAMP8 mice that have found evidence for BBB disruption. For radioactively labeled insulin, we used multiple-time r egression analysis to measure both the unidirectional influx rate (Ki) and the reversible binding to brain endothelium (Vi). A nonsignificant decrease in the transport rate for whole brain occurred in aged SAMP8 mice. Ki and Vi values significantly varied among brain regions and the Ki for the thala mus and the Vi for the cerebellum and thalamus were higher in aged mice. We conclude that alterations in BBB integrity or the activity of the BBB insu lin transporter do not underlie the deficits in learning and memory seen in the aged SAMP8 mouse.