Blood-brain barrier leakage in Alzheimer's disease: From discovery to clinical relevance

Research output: Contribution to journalReview articlepeer-review

6 Scopus citations

Abstract

Alzheimer's disease (AD) is the most common form of dementia. AD brain pathology starts decades before the onset of clinical symptoms. One early pathological hallmark is blood-brain barrier dysfunction characterized by barrier leakage and associated with cognitive decline. In this review, we summarize the existing literature on the extent and clinical relevance of barrier leakage in AD. First, we focus on AD animal models and their susceptibility to barrier leakage based on age and genetic background. Second, we re-examine barrier dysfunction in clinical and postmortem studies, summarize changes that lead to barrier leakage in patients and highlight the clinical relevance of barrier leakage in AD. Third, we summarize signaling mechanisms that link barrier leakage to neurodegeneration and cognitive decline in AD. Finally, we discuss clinical relevance and potential therapeutic strategies and provide future perspectives on investigating barrier leakage in AD. Identifying mechanistic steps underlying barrier leakage has the potential to unravel new targets that can be used to develop novel therapeutic strategies to repair barrier leakage and slow cognitive decline in AD and AD-related dementias.

Original languageEnglish
Article number108119
JournalPharmacology and Therapeutics
Volume234
DOIs
StatePublished - Jun 2022

Bibliographical note

Funding Information:
This project was supported by grant number 2R01AG039621 (to A.M.S.H.) and R01AG075583 (to A.M.S.H. and B.B.) from the National Institute on Aging. The content is solely the authors' responsibility and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health.

Funding Information:
This project was supported by grant number 2R01AG039621 (to A.M.S.H.) and R01AG075583 (to A.M.S.H. and B.B.) from the National Institute on Aging . The content is solely the authors' responsibility and does not necessarily represent the official views of the National Institute on Aging or the National Institutes of Health.

Publisher Copyright:
© 2022 The Author(s)

Keywords

  • Alzheimer's disease
  • Barrier dysfunction
  • Barrier leakage
  • Blood-brain barrier
  • Cerebrovasculature
  • Neurovasculature

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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