Tight junctions of blood-brain barrier in Alzheimer's disease

Abstract

Located along the brain endothelium, the blood-brain barrier (BBB) is essential for regulating the exchange of ions and macromolecules between the blood circulation and neural tissue and restricting brain entry of potentially damaging blood-borne agents. To maintain central nervous system (CNS) homeostasis, brain endothelial cells tightly control entry and exit using specific transporter and receptor proteins for metabolite movement across cells (transcellular transport). In addition, brain endothelial cells are linked by tight junction (TJ) protein complexes that form a tight seal to limit movement between cells (paracellular transport). This has direct relevance to the pathogenesis of Alzheimer disease (AD) where failure to clear the pathogenic amyloid-β (Aβ) peptide across the BBB has been implicated as a key factor in disease progression. Impaired brain clearance of Aβ can also lead to the accumulation of Aβ around cerebral blood vessels, a condition known as cerebral amyloid angiopathy (CAA) that is found in over 80% of AD patients.