Why is the apoe4 gene linked with Alzheimer's risk?

THAT'S THE WHY:WHEN IT comes to genes and the risk of developing a disease, the relationships are seldom clear-cut. But it does seem that carrying a particular type of apolipoprotein E (ApoE) gene is linked with an increased risk of Alzheimer's disease.

The gene codes instructions to make a protein that helps to carry fats in the bloodstream, and it comes in various alleles, or forms. One is ApoE4, and it’s this version that is associated with an increased risk of Alzheimer’s. But why?

A new study in mice has made some interesting findings, which suggest that the ApoE4 gene is involved in a biochemical cascade that results in “leaky” small blood vessels and allows toxins into brain tissue.

Mice with the ApoE4 gene had high levels of a substance called cyclophilin A in cells that help to maintain the “blood-brain barrier” – a protective barrier that can keep toxins out of the brain. The researchers teased out the chain of events in these mice, which also appeared to involve inflammatory molecules and enzymes.

“We are beginning to understand much more about how ApoE4 may be contributing to Alzheimer’s disease,” says researcher Dr Robert Bell from the University of Rochester in a release. “In the presence of ApoE4, increased cyclophilin A causes a breakdown of the cells lining the blood vessels in Alzheimer’s disease in the same way it does in cardiovascular disease or abdominal aneurysm.”

While the study was in mice rather than humans, the paper in the journal Nature comments that understanding the contribution of the gene to the pathogenesis of Alzheimer’s disease may provide an avenue to a new therapy.