Effect of ß-amyloid on blood-brain barrier properties and function.

The deposition of beta-amyloid (Aß) aggregates in the brain, accompanied by impaired cognitive function, is a characteristic feature of Alzheimer's disease (AD). An important role in this process is played by vascular disorders, in particular, a disturbance of the blood-brain barrier (BBB). The BBB controls the entry of Aß from plasma to the brain via the receptor for advanced glycation end products (RAGE) and the removal of brain-derived Aß via the low-density lipoprotein receptor-related protein (LRP1). The balance between the input of Aß to the brain from the periphery and its output is disturbed during AD. Aß changes the redox-status of BBB cells, which in turn changes the functioning of mitochondria and disrupts the barrier function of endothelial cells by affecting tight junction proteins. Aß oligomers have the greatest toxic effect on BBB cells, and oligomers are most rapidly transferred by transcytosis from the brain side of the BBB to the blood side. Both the cytotoxic effect of Aß and the impairment of barrier function are partly due to the interaction of Aß monomers and oligomers with membrane-bound RAGE. AD therapies based on the disruption of this interaction or the creation of decoys for Aß are being developed. The question of the transfer of various Aß isoforms through the BBB is important, since it can influence the development of AD. It is shown that the rate of input of Aß40 and Aß42 from the blood into the brain is different. The actual question of the transfer of pathogenic Aß isoforms with post-translational modifications or mutations through the BBB still remains open.