December 9, 2019

Does a Breached Blood-Brain Barrier Cause Seizures in Alzheimer’s Disease?

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Image credit: Science Translational Medicine/AAAS. Spatially Matched. In a person with epilepsy, areas where the blood-brain barrier is leakiest (left) partially overlap with areas where transient paroxysmal slow-wave events (PSWEs) are more frequent (right).

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 TGF Beta receptors, overexcite neuronal networks, and impair cognition. Breaches correlated with localized 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 TGF Beta antagonist drug prevented slow-wave events and seizures.

“Together, the papers provide a biologically plausible and intriguing mechanism by which a leaky blood-brain barrier could contribute to network hyperexcitability in aging and AD,” wrote Keith Vossel, University of Minnesota, Minneapolis, to Alzforum (see comment below).

“There is a strong emerging story about how blood-brain barrier alterations may trigger a variety of downstream effects that result in inflammation and electrophysiological changes,” wrote Bill Jagust, University of California, Berkeley, to Alzforum. “How this relates to Alzheimer’s disease is still something we need to work out.” Jagust was not involved in the current work.

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