A new study has revealed clues to how the Alzheimer’s risk gene APOE4 can damage blood vessels in the brain and identified potential new ways to prevent the damage. The research is published online on 16 May in the journal Nature.
There are three different versions of the APOE gene in the population, with people who carry the APOE4 version having a higher risk of developing Alzheimer’s. The researchers looked at the effect of APOE4 on the ‘blood-brain barrier’, a shield of tightly connected cells which carefully regulates which proteins can pass into the brain.
The study found that the blood-brain barrier is damaged in mice that carry APOE4, reducing blood flow and allowing potentially harmful proteins to enter the brain. A few months later, nerve cells in the brains of these mice also started to become unhealthy and less responsive.
Mice that carried APOE4 were found to have around five-fold higher levels of an inflammatory protein called cyclophilin A in the cells of the blood-brain barrier. Cyclophilin A was found to activate a molecular chain of events which caused the cells of the barrier to break apart and become leaky.
When the scientists used a drug to block the effect of cyclophilin A or to prevent the chain of events that it triggers, the damage was reversed and the blood-brain barrier remained intact. This blocked the harmful proteins from entering brain, while nerve cells remained healthy and active.
Dr Simon Ridley, Head of Research at Alzheimer’s Research UK, said:
“The causes of Alzheimer’s are complex, and while we know that APOE4 is a risk factor for the disease, a lot remains to be understood about how the gene works. This study in mice provides clues to how APOE4 could contribute to Alzheimer’s by damaging blood vessels in the brain and highlights potential targets for treatment.
“Whilst this research is in its early stages, understanding Alzheimer’s and identifying targets for the development of new treatments is absolutely vital. With over half a million people across the UK living with Alzheimer’s, we must invest in research if we are to make the progress that is so desperately needed.”