Abstract Decreased beta-amyloid clearance in Alzheimer’s disease and increased blood-brain
barrier permeability in aged subjects have been reported in several articles. However,
morphological and functional characterization of blood-brain barrier and its membrane
transporter activity have not been described in physiological aging yet. The aim of
our study was to explore the structural changes in the brain microvessels and possible
functional alterations of P-glycoprotein at the blood-brain barrier with aging. Our
approach included MR imaging for anatomical orientation in middle aged rats, electronmicroscopy
and immunohistochemistry to analyse the alterations at cellular level, dual or triple-probe
microdialysis and SPECT to test P-glycoprotein functionality in young and middle aged
rats. Our results indicate that the thickness of basal lamina increases, the number
of tight junctions decreases and the size of astrocyte endfeet extends with advanced
age. On the basis of microdialysis and SPECT results the P-gp function is reduced
in old rats. With our multiparametric approach a complex regulation can be suggested
which includes elements leading to increased permeability of blood-brain barrier by
enhanced paracellular and transcellular transport, and factors working against it.
To verify the role of P-gp pumps in brain aging further studies are warranted.
