High levels of iron in the brain could increase the risk of developing Alzheimer’s disease and hasten the cognitive decline that comes with it, new research suggests.
The results of the study, which tracked the brain degeneration of people with Alzheimer’s over a seven-year period, suggest it might be possible to halt the disease with drugs that reduce iron levels in the brain.
“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.”
Alzheimer’s is a devastating disease that researchers suspect “begins when two abnormal protein fragments, known as plaques and tangles, accumulate in the brain and start killing our brain cells,” explains Fiona Macdonald for ScienceAlert.
It starts by destroying the hippocampus – the region of the brain where memories are formed and stored – and eventually damages the region where language is processed, making it difficult for advanced Alzheimer’s patients to communication. As the disease’s gradual takeover continues, people lose the ability to regulate their emotions and behaviour, and to make sense of the world around them.
But previous studies have shown that people with Alzheimer’s disease also have elevated levels of brain iron, which may also be a risk factor for the disease.
“There has been debate for a long period of time whether this is important or whether it’s just a coincidence,” Ayton told ABC Science.
The long-term impact of elevated iron levels on the disease outcome has not been investigated, the researchers say.
So Ayton’s team decided to test this, examining the link between brain iron levels and cognitive decline in three groups of people over seven years. The participants included 91 people with normal cognition, 144 people with mild cognitive impairment, and 67 people with diagnosed Alzheimer’s disease.
At the beginning of the study, the researchers determined the patients’ brain iron levels by measuring the amount of ferritin in the cerebrospinal fluid around the brain. Ferritin is a protein that stores and releases iron.
The researchers did regular tests and MRI scans to track cognitive decline and changes in the brain over the study period.
They found that people with higher levels of ferritin – in all groups – had faster declines in cognitive abilities and accelerated shrinking of the hippocampus. Levels of ferritin were also a linked to a greater likelihood of people with mild cognitive impairment developing Alzheimer’s.
Their data contained some other interesting takeaways: The researchers found higher levels of ferritin corresponded to earlier ages for diagnoses – roughly three months for every 1 nanogram per millilitre increase.
They also found that people with the APOE-e4 gene variant, which is known to be the strongest genetic risk factor for the disease, had the highest levels of iron in their brains.
This suggests that APOE-e4 may be increasing Alzheimer’s disease risk by increasing iron levels in the brain, Ayton told ABC Science.
The researchers say their findings, which were published in the journal Nature Communications, justify the revival of clinical trials to explore drugs to target brain iron levels.
In a study carried out 24 years ago, a drug called deferiprone halved the rate of Alzheimer’s cognitive decline, Ayton told Clare Wilson at NewScientist. “Perhaps it’s time to refocus the field on looking at iron as a target.”
“Lowering CSF ferritin, as might be expected from a drug like deferiprone, could conceivably delay mild cognitive impairment conversion to Alzheimer’s disease by as much as three years,” the team wrote.