Does a Breached Blood-Brain Barrier Cause Seizures in AD?

Post from the Alz Forum

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In back-to-back papers in the December 4 Science Translational Medicine, scientists led by Daniela Kaufer, University of California, Berkeley, and Alon Friedman, Ben-Gurion University of the Negev, Beer-Sheva, Israel, report that age-related cracks in the blood-brain barrier allow an influx of serum protein albumin into the brain, where they activate TGFβ receptors, overexcite neuronal networks, and impair cognition. Breaches correlated with localised slowing of cortical activity in epilepsy, Alzheimer’s disease patients, and in mouse models of AD. Called paroxysmal slow-wave events, these activity changes correlated with cognitive impairment and interspersed with seizures in epilepsy patients.

The findings suggest that, in some people with AD, silent seizures may be due to a leaky BBB, and that this may explain some of their cognitive decline. In rodents, a TGFβ antagonist drug prevented slow-wave events and seizures.

  • As people age, their blood-brain barriers become leakier.
  • This fuels astrocytic TGFβ signaling, hyperexcitation, memory loss.
  • In mice, a TGFβ inhibitor prevents these problems.

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