Growing Evidence That Infections May Drive Alzheimer’s

Researchers at the University of Southampton will present research today suggesting that inflammation in the brain caused by systemic infections could drive the development of Alzheimer’s disease. The findings will be presented at the Alzheimer’s Research UK Annual Conference 2014 in Oxford, the largest dementia research conference in the UK.

The brain, like other areas of the body, contains immune cells poised and ready to mobilise in response to injury or damage. These cells have a wide variety of roles and can act both to ramp up the immune reaction by triggering inflammation, and to dampen down this defensive response. The balance of pro- and anti-inflammatory messages is important for maintaining a healthy brain environment.

Previous research, some completed at the University of Southampton, has found that neurodegenerative diseases like Alzheimer’s, Parkinson’s and prion diseases trigger an immune response in the brain. However, scientists continue to debate whether this immune response is protective or could cause these diseases to get worse.

The team of researchers, led by Prof Hugh Perry, has been studying inflammation in mice that develop a neurodegenerative disease similar to CJD in humans. This disease causes progressive nerve cell damage in the brain similar to that seen in Alzheimer’s and Parkinson’s. The researchers have been looking closely at the behaviour of immune cells in the brain and their role in the development of this disease in mice.

Their findings show that early in the disease, immune cells in the brain appear to respond as a defence mechanism against the progressive damage to nerve cells. However, if the mice have a systemic infection at the same time, the immune cells switch roles, ramping up the levels of pro-inflammatory molecules in the brain and making the disease worse.

Prof Hugh Perry, Professor of Experimental Neuropathology, led the study in collaboration with Prof Clive Holmes. He said:

“We observed that inflammation in the body triggered a stark change in the behaviour of immune cells in the brains of the mice. Having a systemic infection or inflammatory disease – one that affects the body rather than the brain – was enough to change how these cells to respond to the disease in the brain. Rather than defending the brain against the developing disease, brain immune cells were ‘primed’ by the ongoing neurodegeneration and ramped up levels of inflammation, causing even more damage.

“The findings mirror what we are observing in people with Alzheimer’s disease in the clinic. We have found evidence that people with Alzheimer’s who have systemic infections, such as chest or urine infections, are more likely to have faster decline in memory and thinking and more severe symptoms.”

The team hopes that by understanding the molecular mechanisms controlling this switch in immune cell behaviour, they can harness these changes to develop new treatments. They have already identified several proteins involved in the priming of immune cells in the brain.

Prof Perry said:

“We are now looking at whether our findings could provide a new way-in to developing treatments to modify this altered immune response and the communication between peripheral inflammation and primed immune cells in the brain. If this process is key to driving diseases like Alzheimer’s, then keeping it in check could be a way to slow down the disease in people.”

Dr Eric Karran, Head of Research at Alzheimer’s Research UK, said:

“We are pleased to see these important early findings discussed at the conference today. There is growing research evidence implicating inflammation in diseases like Alzheimer’s and we urgently need to understand the role it plays in more detail.

“It is promising to see that observations made in the clinic are being following up with more detailed molecular analysis. We hope that further research will pinpoint culprit proteins involved in inflammation that could be used as a target for treatment development. With half a million people in the UK living with Alzheimer’s, the need for effective treatments has never been greater.”




















COTS 2024