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

Axel Montagne, Zhen Zhao, Berislav V Zlokovic

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish
Pages (from-to)3151-3169
Number of pages19
JournalJournal of Experimental Medicine
Volume214
Issue number11
DOIs
Publication statusPublished - 6 Nov 2017

Keywords

  • Alzheimer Disease/genetics
  • Amyloid beta-Protein Precursor/genetics
  • Animals
  • Blood-Brain Barrier/metabolism
  • Disease Models, Animal
  • Humans
  • Mice, Transgenic
  • Mutation
  • Presenilin-1/genetics
  • tau Proteins/genetics

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