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A cell infected with herpes virus

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

A major hallmark of Alzheimer’s disease is the build-up of protein clumps in the brain 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 Alzheimer’s disease. People with HSV-1 are more likely to get Alzheimer’s disease, and high levels of herpes viruses have been found in the brains of people who died with the condition.

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To understand how HSV-1 might cause Alzheimer’s disease, Dana Cairns at Tufts University in the US, and her colleagues added the virus to clumps of brain tissue grown in dishes. They made the mini-brains by filling donut-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 Alzheimer’s disease. They 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 that is currently underway in the US testing whether valacyclovir helps to treat Alzheimer’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. People 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 like Porphyromonas gingivalis, a bacterium that has been linked with Alzheimer’s and gum disease – also cause plaque formation in their brain models.

Journal reference: Science Advances, DOI: 10.1126/sciadv.aay8828

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