People carrying the Alzheimer’s risk gene APOE4 are more likely to develop the neurological disease because they have trouble clearing the amyloid plaques characteristic of the illness say researchers in Southampton.
The APOE gene is the biggest known genetic factor for late-onset Alzheimer’s disease, and those carrying the APOE4 version are at a higher risk of developing the disease at an earlier age than those carrying APOE2 or APOE3.
People with APOE4 have higher levels of amyloid – a toxic protein – in blood vessels in their brain, causing a condition called cerebral amyloid angiopathy (CAA). CAA may contribute to Alzheimer’s and researchers from the University of Southampton set about investigating this link.
Using normal mice and mice bred to have human versions of either APOE4 or APOE3 – its neutral equivalent – researchers examined the effect of the risk gene in the brain. They looked at the level of amyloid in the blood vessels using fluorescently labelled versions of the protein which they could track.
“We found that only the mice with APOE4 had high levels of amyloid in the blood vessels of their brain, suggesting that people with the risk gene may not be able to clear the toxic protein as effectively from their brain,” said Dr Cheryl Hawkes. “After delving a little deeper, we discovered that the blood vessels in mice with APOE4 were very different – they were made up of a different set of components that may not work as well to clear amyloid.”
“These initial results are really exciting because they help us to build a bigger picture of the factors influencing a person’s risk of Alzheimer’s. The next step will be to move this study from mice to humans to confirm that we see a similar change.”
The study – funded by Alzheimer’s Research UK – was published in PLoS ONE.