Alzheimer's disease and blood-brain barrier function-Why have anti-beta-amyloid therapies failed to prevent dementia progression?

Neurosci Biobehav Rev. 2009 Jul;33(7):1099-108. doi: 10.1016/j.neubiorev.2009.05.006. Epub 2009 May 27.


Proteopathies of the brain are defined by abnormal, disease-inducing protein deposition that leads to functional abrogation and death of neurons. Immunization trials targeting the removal of amyloid-beta plaques in Alzheimer's disease have so far failed to stop the progression of dementia, despite autopsy findings of reduced plaque load. Here, we summarize current knowledge of the relationship between AD pathology and blood-brain barrier function, and propose that the activation of the excretion function of the blood-brain barrier might help to achieve better results in trials targeting the dissolution of cerebral amyloid-beta aggregates. We further discuss a possible role of oligomers in limiting the efficacy of immunotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / therapy*
  • Amyloid beta-Peptides / immunology
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / physiopathology*
  • Cost of Illness
  • Disease Progression
  • Humans
  • Immunotherapy*
  • Neurodegenerative Diseases / physiopathology
  • Prevalence


  • ATP-Binding Cassette Transporters
  • Amyloid beta-Peptides