Apolipoprotein E, amyloid-β, and blood-brain barrier permeability in Alzheimer disease

There is increasing evidence for blood-brain barrier (BBB) compromise in Alzheimer disease (AD). The presence of the epsilon 4 allele of the apolipoprotein E (apoE) gene is a risk factor for sporadic AD. Apolipoprotein E is essential both for maintenance of BBB integrity and for the deposition of fibrillar amyloid-beta (A beta) that leads to the development of A beta plaques in AD and to cerebral amyloid angiopathy. This review investigates the relationships between apoE, A beta, and the BBB in AD. Alterations in the expression and distribution of the BBB A beta transporters receptor for advanced glycation end-products and low-density lipoprotein receptor-related protein 1 in AD and the potential roles of apoE4 expression in adversely influencing A beta burden and BBB permeability are also examined. Because both apoE and A beta are ligands for low-density lipoprotein receptor-related protein 1, all 3 molecules are present in AD plaques, and most AD plaques are located close to the cerebral microvasculature. The interactions of these molecules at the BBB likely influence metabolism and clearance of A beta and contribute to AD pathogenesis. Therapeutic alternatives targeting apoE/A beta and sealing a compromised BBB are under development for the treatment of AD.