Iron in the brain boosts Alzheimer's risk
The findings, published in in , suggest it might be possible to arrest the disease using drugs that remove iron from the brain.
"We think that iron is contributing to the disease progression of Alzheimer's disease," says neuroscientist Dr Scott Ayton from the University of Melbourne.
"This is strong evidence to base a clinical trial on lowering iron content in the brain to see if that would impart a cognitive benefit."
Ayton says iron was first implicated in Alzheimer's disease in the 1950s, following post mortem studies showing higher iron levels in the brains of those with the disease.
"But there has been debate for a long period of time whether this is important or whether it's just a coincidence," says Ayton.
To help settle this question, Ayton and colleagues studied the link between iron and Alzheimer's disease in three groups of people: 91 people with normal cognition; 144 people with mild cognitive impairment; and 67 people with Alzheimer's disease.
At the beginning of the study, the researchers measured the iron binding protein, ferritin, in cerebrospinal fluid that surrounds the brain, as a proxy for iron levels in the brain.
Over the next seven years they carried out regular cognitive tests and took MRI brain scans to look for degeneration in the brain.
In all three groups, those with high levels of ferritin had poorer cognition over the study period, had accelerated shrinkage of the hippocampus -- part of the brain involved in consolidating memories -- and were more likely to progress to Alzheimer's disease.
In the first study to quantify the effect of iron on Alzheimer's risk, Ayton and colleagues found that every 1 nanogram per millilitre increase in ferritin levels resulted in the the onset of Alzheimer's occurring three months earlier.
Ayton says the concentration of ferritin was at least as good at predicting progression to Alzheimer's as more traditional biomarkers, such as beta amyloid protein and tau protein.
Interestingly, the researchers found that those with the APOE-e4 gene variant, which is known to be the strongest risk factor for Alzheimer's after ageing, had the highest levels of ferritin in their cerebrospinal fluid.
This suggests that APOE-e4 may be increasing Alzheimer's disease risk by increasing iron levels in the brain, says Ayton.
Drug targets
Most Alzheimer's drugs try to stop the formation of plaque in the brain, caused by beta amyloid.
But so far, says Ayton, after 10 phase III clinical trials, this strategy has not worked.
Ayton suggests instead that it would be better to stop the build up of iron.
Just as there are drugs to remove excess iron in people with beta-thalassemia, he says there are safe drugs that could be used remove iron from the brain.
Ayton says the study also compared the levels of iron in the blood with that in the brain, and the findings suggest people should not worry about their iron intake.
Diet, iron supplements and giving blood would not alter the amount of iron in the brain, he says.
"Our evidence suggests that the amount of iron in the rest of your body doesn't affect the iron levels in your brain."
0 reacties:
Post a Comment