Alzheimer's disease and the blood-brain barrier: Past, present and future

Successful prevention and treatment of late-onset Alzheimer's disease (AD) is a high priority for industrialized societies where the incidence is growing rapidly. Much of the underlying biology leading to AD is unknown, and the more knowledge we gain the more we appreciate the complexities involved. Popular etiologic hypotheses have largely ignored the blood-brain barrier (BBB) as an important factor contributing to the pathologic hallmarks of this most common form of dementia. Evidence idenfying BBB dysfunction in AD or patients at risk (i.e. those with mild cognitive impairment) continue to escalate. This review highlights methodological issues facing investigators assessing BBB integrity in living patients while also discussing whether the BBB dysfunction is a cause, effect or epiphenomenon in AD. Rationale for future research pursuits aimed at describing the role of BBB function in AD pathogenesis is also presented.