The deposition of beta-amyloid (Aβ) 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 Aβ from plasma to the brain via the receptor for advanced glycation end products (RAGE) and the removal of brain-derived Aβ via the low-density lipoprotein receptor-related protein (LRP1). The balance between the input of Aβ to the brain from the periphery and its output is disturbed during AD. Aβ 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. Aβ 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 Aβ and the impairment of barrier function are partly due to the interaction of Aβ monomers and oligomers with membrane-bound RAGE. AD therapies based on the disruption of this interaction or the creation of decoys for Aβ are being developed. The question of the transfer of various Aβ isoforms through the BBB is important, since it can influence the development of AD. It is shown that the rate of input of Aβ40 and Aβ42 from the blood into the brain is different. The actual question of the transfer of pathogenic Aβ isoforms with post-translational modifications or mutations through the BBB still remains open.
Keywords: Beta-amyloid; Blood-brain barrier; LRP1; Mitochondria; RAGE; Redox status.
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