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Amyloid β Oligomers Disrupt Blood-CSF Barrier Integrity by Activating Matrix Metalloproteinases.

Marjana BrkicSriram BalusuElien Van WonterghemNina GorléIryna BenilovaAnna KremerInge Van HoveLieve MoonsBart De StrooperSelma KanazirClaude LibertRoosmarijn E. Vandenbroucke
Published in: The Journal of neuroscience : the official journal of the Society for Neuroscience (2016)
No treatments are yet available to cure Alzheimer's disease; however, soluble Aβ oligomers are believed to play a crucial role in the neuroinflammation that is observed in this disease. Here, we studied the effect of Aβ oligomers on the often neglected barrier between blood and brain, called the blood-CSF barrier (BCSFB). This BCSFB is formed by the choroid plexus epithelial cells and is important in maintaining brain homeostasis. We observed Aβ oligomer-induced changes in morphology and loss of BCSFB integrity that might play a role in Alzheimer's disease progression. Strikingly, both inhibition of matrix metalloproteinase (MMP) activity and MMP3 deficiency could protect against the detrimental effects of Aβ oligomer. Clearly, our results suggest that MMP inhibition might have therapeutic potential.
Keyphrases
  • resting state
  • white matter
  • cell migration
  • cerebral ischemia
  • cognitive decline
  • traumatic brain injury
  • functional connectivity
  • lipopolysaccharide induced
  • subarachnoid hemorrhage