Ailing bodies can harm the mind (Image: Elisabeth Rull/Picture Tank)

HERE’S another reason to be fit and healthy. Staying free of “lifestyle diseases” and infections could put the brakes on Alzheimer’s.

The advice comes from teams that have pieced together how these bodily ailments create inflammation that ultimately spills over into the brain, sending its immune cells into a hyperactive, destructive state.

“The idea is simple: monitoring and prompt treatment [of inflammation] could prevent the decline from Alzheimer’s,” said Hugh Perry of the University of Southampton, UK, as he presented the research at the Alzheimer’s Research UK annual meeting in Oxford last month.


Monitoring and prompt treatment of inflammation could prevent the decline seen in Alzheimer’s

As well as revealing step by step how disease and infection can aggravate and accelerate the early stages of Alzheimer’s, Perry and his colleague Clive Holmes have begun a pioneering trial in 40 people to see if a drug that acts to dampen inflammation in the body can help delay the progress of the brain disease. Etanercept is already prescribed to people with rheumatoid arthritis, and works by sponging up a molecule that aggravates inflammation.

According to Alzheimer’s Disease International, 44 million people globally have dementia, of which Alzheimer’s is the most common type. The beginnings of the disease are characterised by the appearance in the brain of plaques of amyloid proteins and tangles of tau proteins. They prompt the brain’s native immune cells, the microglia, to multiply in a bid to dispose of the troublesome new debris.

The downside of this heightened state is that it also makes the microglia unusually sensitive to any other signs of trouble – for example, signals sent to the brain as a result of bodily inflammation. This stirs up the microglia even further, tipping them into a hyperactive state in which they attack healthy neurons, boosting the progression of Alzheimer’s.

Now Perry and Holmes have built up a detailed picture of how this happens through experiments in mice with prion disease, a model of neurodegeneration. They show that as the disease develops, two inflammatory molecules produced in the brain – proteins called interleukin 34 and colony-stimulating factor-1 – activate the microglia.

Other inflammatory molecules that provoke the microglia are made by the white blood cells that gobble up bacteria and other sources of infection in the body. These cells are overactive in conditions of chronic inflammation such as diabetes, atherosclerosis and obesity.

Once these alarm signals reach the surfaces of blood vessels lining the brain, the microglia produce a neurotoxic molecule called interleukin-1 beta. This is followed by a mass die-off of neurons and a lasting decline in memory and other cognitive abilities (Nature Reviews Neurology, doi.org/sc8).

Separate work by Colm Cunningham and his colleagues at Trinity College Dublin in Ireland has shown that interleukin-1 beta is a likely neuron-killing culprit, along with other inflammatory molecules called prostaglandins (Journal of Neuroscience, doi.org/sdr). They have also shown that taking a type of anti-inflammatory drug can prevent the cognitive decline in mice produced by this cascade of inflammatory events.

The results of Perry and Holmes’s human trial of etanercept – also an anti-inflammatory – are expected later this year. The hope is that the drug will delay the progression of Alzheimer’s. If it is found to, the results will bolster the theory that combating infection and chronic inflammation in the body is an effective strategy to keep Alzheimer’s at bay.

It’s an attractive theory because it implies that the disease could be slowed with drugs that work outside the brain. Recent research has focused on combating the plaques and tangles in the brain, with disappointing results. “They are clearly not irrelevant, but patients continue to get worse even if the plaques are cleared,” says Cunningham.

The inflammation theory is also making sense to other teams. “We’re already looking at the role of microglia as a causal factor linking diabetes to Alzheimer’s,” says Ewan McNay of the University at Albany in New York.

So can people help themselves steer clear of Alzheimer’s by adopting lifestyles that avoid inflammatory disease? “We know that exercise and a healthy diet that avoids obesity and diabetes are sensible strategies for other aspects of our health. Emerging data suggest this will also slow brain decline,” says Cunningham. “Actively treating bodily inflammation in middle age and beyond may lessen the effects of these conditions on the brain’s decline in old age.”

This article appeared in print under the headline “Keep the body well to slow Alzheimer’s”