PMC

The main functions of the BBB: Substances can enter the brain by extracellular, saturable influx, and lipid solubility (transmembrane diffusion) pathways. Cells enter by diapedesis. The physical barrier formed by the capillary wall, saturable efflux systems, enzymatic activity at the barrier cells, and CSF reabsorption limit uptake and retention of substances by the CNS. The barrier cells also secrete a number of substances into brain and blood.

Three ways discussed in this review in which the BBB is relevant to Alzheimer’s disease with examples. Endothelial cell #1: Dysfunctions of BBB can promote AD as exemplified here by impaired efflux of A-beta from brain. Endothelial cell #2: Drugs needed to treat AD must cross the BBB as exemplified here by the ability of donepezil to be transported across the BBB. Endothelial cell #3: Alterations in BBB means that delivery of drugs to the CNS for non-AD conditions (pain control, depression, delirium) is different than in non-AD patients as exemplified by impaired P-gp function.