Alzheimer's disease drug development and the problem of the blood‐brain barrier

Alzheimer's disease (AD) drug development is limited by the presence of the blood‐brain barrier (BBB). More than 98% of all small‐molecule drugs, and ∼100% of all large‐molecule drugs, do not cross the BBB. Although the vast majority of AD drug candidates do not cross the BBB, the present‐day AD drug‐development effort is characterized by an imbalance wherein >99% of the drug‐development effort is devoted to central nervous system (CNS) drug discovery, and <1% of drug development is devoted to CNS drug delivery. Future AD drug development needs a concerted effort to incorporate BBB sciences early in the CNS drug discovery process. This goal can be achieved by a reallocation of resources, and an expansion of research efforts in the pure science of BBB biology and the applied science of brain drug‐targeting technology.