Alison Abbot in Nature:
Neuroscientist Michael Heneka knows that radical ideas require convincing data. In 2010, very few colleagues shared his belief that the brain’s immune system has a crucial role in dementia. So in May of that year, when a batch of new results provided the strongest evidence he had yet seen for his theory, he wanted to be excited, but instead felt nervous. He and his team had eliminated a key inflammation gene from a strain of mouse that usually develops symptoms of Alzheimer’s disease. The modified mice seemed perfectly healthy. They sailed through memory tests and showed barely a sign of the sticky protein plaques that are a hallmark of the disease. Yet Heneka knew that his colleagues would consider the results too good to be true.
Even he was surprised how well the mice fared; he had expected that removal of the gene, known as Nlpr3, would protect their brains a little, but not that it would come close to preventing dementia symptoms. “I thought something must have gone wrong with the experiments,” says Heneka, from the German Center for Neurodegenerative Diseases in Bonn. He reanalysed the results again and again. It was past midnight when he finally conceded that they might actually be true. Over the next couple of years, he confirmed that nothing had gone wrong with the experiments. Together with his colleagues, he replicated and elaborated on the results1. Since then, numerous studies have bolstered the link between dementia and the brain’s immune system, highlighting the cells and signals involved2. But none has managed to fully pin it down — the link seems to be slippery and dynamic, changing as the disease progresses.