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Neurovascular Alterations in Alzheimer’s Disease: Transporter Expression Profiles and CNS Drug Access

  • Review Article
  • Theme: CNS Barriers in Health and Disease
  • Published:
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Abstract

Despite a century of steady and incremental progress toward understanding the underlying biochemical mechanisms, Alzheimer’s disease (AD) remains a complicated and enigmatic disease, and greater insight will be necessary before substantive clinical success is realised. Over the last decade in particular, a large body of work has highlighted the cerebral microvasculature as an anatomical region with an increasingly apparent role in the pathogenesis of AD. The causative interplay and temporal cascade that manifest between the brain vasculature and the wider disease progression of AD are not yet fully understood, and further inquiry is required to properly characterise these relationships. The purpose of this review is to highlight the recent advancements in research implicating neurovascular factors in AD, at both the molecular and anatomical levels. We begin with a brief introduction of the biochemical and genetic aspects of AD, before reviewing the essential concepts of the blood-brain barrier (BBB) and the neurovascular unit (NVU). In detail, we then examine the evidence demonstrating involvement of BBB dysfunction in AD pathogenesis, highlighting the importance of neurovascular components in AD. Lastly, we include within this review research that focuses on how altered properties of the BBB in AD impact upon CNS exposure of therapeutic agents and the potential clinical impact that this may have on people with this disease.

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Acknowledgements

Mitchell P. McInerney is supported by an Australian Government Research Training Program Scholarship.

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Authors and Affiliations

  1. Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, VIC, 3052, Australia

    Mitchell P. McInerney & Joseph A. Nicolazzo

  2. Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052, VIC, Australia

    Jennifer L. Short

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  1. Mitchell P. McInerney
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Correspondence to Joseph A. Nicolazzo.

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McInerney, M.P., Short, J.L. & Nicolazzo, J.A. Neurovascular Alterations in Alzheimer’s Disease: Transporter Expression Profiles and CNS Drug Access. AAPS J 19, 940–956 (2017). https://doi.org/10.1208/s12248-017-0077-5

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