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J Exp Med. 2017 Nov 6;214(11):3151-3169. doi: 10.1084/jem.20171406. Epub 2017 Oct 23.

Alzheimer's disease: A matter of blood-brain barrier dysfunction?

Author information

1
Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, CA.
2
Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, Los Angeles, CA.

Abstract

The blood-brain barrier (BBB) keeps neurotoxic plasma-derived components, cells, and pathogens out of the brain. An early BBB breakdown and/or dysfunction have been shown in Alzheimer's disease (AD) before dementia, neurodegeneration and/or brain atrophy occur. However, the role of BBB breakdown in neurodegenerative disorders is still not fully understood. Here, we examine BBB breakdown in animal models frequently used to study the pathophysiology of AD, including transgenic mice expressing human amyloid-β precursor protein, presenilin 1, and tau mutations, and apolipoprotein E, the strongest genetic risk factor for AD. We discuss the role of BBB breakdown and dysfunction in neurodegenerative process, pitfalls in BBB measurements, and how targeting the BBB can influence the course of neurological disorder. Finally, we comment on future approaches and models to better define, at the cellular and molecular level, the underlying mechanisms between BBB breakdown and neurodegeneration as a basis for developing new therapies for BBB repair to control neurodegeneration.

PMID:
29061693
PMCID:
PMC5679168
DOI:
10.1084/jem.20171406
[Indexed for MEDLINE]
Free PMC Article

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