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Mini-brains grown in a dish rapidly develop signs of ´¡±ô³ú³ó±ð¾±³¾±ð°ù’s disease when infected with the common herpes virus that causes cold sores. The finding adds to growing evidence that some cases of ´¡±ô³ú³ó±ð¾±³¾±ð°ù’s are triggered by viruses and could potentially be treated with antiviral drugs.

A major hallmark of ´¡±ô³ú³ó±ð¾±³¾±ð°ù’s disease is the build-up in the brain of protein clumps called beta-amyloid plaques. An emerging school of thought is that these plaques function as defences against viruses and bacteria that sometimes manage to get into the brain.

Herpes simplex virus-1 (HSV-1), which causes cold sores and stays in the body for life, is one virus that has been linked to ´¡±ô³ú³ó±ð¾±³¾±ð°ù’s disease. People with HSV-1 are more likely to get ´¡±ô³ú³ó±ð¾±³¾±ð°ù’s, and high levels of herpes viruses have been found in the brains of people who died with the condition.

To understand how HSV-1 might cause ´¡±ô³ú³ó±ð¾±³¾±ð°ù’s disease, Dana Cairns at Tufts University in Massachusetts and her colleagues added the virus to clumps of brain tissue grown in dishes. They made the mini-brains by filling doughnut-shaped scaffolds with human stem cells that were then coaxed into forming brain cells.

Rapid damage

Within three days of being infected with HSV-1, the mini-brains developed large beta-amyloid plaques reminiscent of those found in the brains of people with ´¡±ô³ú³ó±ð¾±³¾±ð°ù’s disease. The mini-brains also showed other signs of the condition, such as inflammation and loss of brain cells.

In contrast, when the mini-brains were treated with valacyclovir, a commonly used herpes drug, they seemed to be protected against HSV-1 damage. This finding lends support to a clinical trial currently under way in the US that is testing whether valacyclovir helps to treat ´¡±ô³ú³ó±ð¾±³¾±ð°ù’s disease in people who also have HSV-1, says Cairns.

One unresolved question is why HSV-1, which is found in about two-thirds of people under 50, seems to invade the brains of some people but not others. Those with weaker blood-brain barriers due to age or genetic factors may be more at risk, says Cairns.

Cairns and her colleagues now hope to test whether other microbes, such as Porphyromonas gingivalis, a bacterium that has been linked with ´¡±ô³ú³ó±ð¾±³¾±ð°ù’s and gum disease, also cause plaque formation in their brain models.

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