Prazosin prevents memory decline in mouse model of Alzheimer's disease, a study has found.

Fast and effective communication between brain cells is essential for the normal functioning of the brain and is orchestrated by chemical messengers called neurotransmitters. The neurotransmitter noradrenaline, as well as several others, can become disrupted in particular areas of the brain during Alzheimer’s. Although best known for stimulating the brain in times of stress, noradrenaline has a range of functions in the brain, including roles in memory, inflammation and the immune system.

The team set out to investigate whether drugs that affect the action of noradrenaline could provide benefits in mice showing features of Alzheimer’s. They tested a range of compounds in the laboratory and found that the drug prazosin, which can be used to relax blood vessels in people with high blood pressure, also showed potential for reducing signs of Alzheimer’s.

The researchers then used the drug to treat mice bred to develop a build-up of the Alzheimer’s protein amyloid in their brain. These mice show a decline in memory performance which is characteristic of the disease in humans. The team found that treatment with prazosin could prevent the memory problems seen in untreated mice.

The drug did not reduce levels of the amyloid protein, but did appear to affect levels of inflammation in the brain. Prazosin boosted the number of brain support cells called astrocytes, which can produce anti-inflammatory proteins.

Dr Magdalena Sastre, from the Department of Medicine at Imperial College London, said: “We are really excited about these findings and the potential they may hold for the future. There is still a lot for us to understand about why prazosin may have benefits in the brain. We think the drug may stimulate an anti-inflammatory response, and there is increasing evidence that inflammation is a key process in Alzheimer’s.”

Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, said: “These promising results are still at an early stage, but research into potential new treatments is vital in the fight to defeat dementia. Brain inflammation is coming under increasing scrutiny in the search for Alzheimer’s treatments, so we are pleased to have funded this study in an important area. Further work will be needed to see how the results translate in people, but it is a real step in the right direction.

“By developing new drugs or looking for undiscovered potential in existing drugs, scientists hope to find effective ways to halt the disease. There are currently no treatments available which slow or stop Alzheimer’s, which is why increased funding for dementia research is so incredibly important.“

Professor Clive Ballard, Director of Research at Alzheimer’s Society, said: “We have known for some time that lifestyle factors such as high blood pressure are linked to dementia. This important research paves the way for further investigation into whether drugs like prazosin could form part of the picture.

“There are 800,000 people living with dementia in the UK. This year the Prime Minister committed to doubling government investment in dementia research. We must now make sure that this money is spent effectively to help people to live well with dementia today and ultimately find a cure.”

Reference

L Katsouri et al. ‘Prazosin, an α1-adrenoceptor antagonist, prevents memory deterioration in the APP23 transgenic mouse model of Alzheimer's disease.’ Neurobiology of Aging, 16 October 2012. doi:10.1016/j.neurobiolaging.2012.09.010