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Adv Drug Deliv Rev. 2018 Oct;135:62-74. doi: 10.1016/j.addr.2018.04.009. Epub 2018 Apr 14.

Impact of aging, Alzheimer's disease and Parkinson's disease on the blood-brain barrier transport of therapeutics.

Author information

1
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, Victoria 3052, Australia.
2
Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, 399 Royal Parade, Parkville, Victoria 3052, Australia. Electronic address: joseph.nicolazzo@monash.edu.

Abstract

Older people are at a greater risk of medicine-induced toxicity resulting from either increased drug sensitivity or age-related pharmacokinetic changes. The scenario is further complicated with the two most prevalent age-related neurodegenerative diseases, Alzheimer's disease (AD) and Parkinson's disease (PD). With aging, AD and PD, there is growing evidence of altered structure and function of the blood-brain barrier (BBB), including modifications to tight junctions and efflux transporters, such as P-glycoprotein. The subsequent impact on CNS drug exposure and risk of neurotoxicity from systemically-acting medicines is less well characterized. The purpose of this review, therefore, is to provide an overview of the multiple changes that occur to the BBB as a result of aging, AD and PD, and the impact that such changes have on CNS exposure of drugs, based on studies conducted in aged rodents or rodent models of disease, and in elderly people with and without AD or PD.

KEYWORDS:

Aging; Alzheimer's disease; Blood-brain barrier; Neurodegenerative disease; P-glycoprotein; Parkinson's disease

PMID:
29665383
DOI:
10.1016/j.addr.2018.04.009

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