Studies have suggested that people with Alzheimer’s also have higher iron levels in their brains. Now it seems that high iron may hasten the disease’s onset.
Researchers at the University of Melbourne in Australia followed 144 older people who had mild cognitive impairment for seven years. To gauge how much iron was in their brains, they measured ferritin, a protein that binds to the metal, in their cerebrospinal fluid. For every nanogram per millilitre people had at the start of the study, they were diagnosed with Alzheimer’s on average three months earlier.
The team also found that the biggest risk gene for Alzheimer’s, ApoE4, was strongly linked with higher iron, suggesting this is why carrying the gene makes you more vulnerable.
CSF ferritin associates with ApoE levels and varies according to APOE genotype.
The finding by itself doesn’t prove that reducing iron levels would cut people’s risk of Alzheimer’s but a trial of a drug that rids the body of some of its iron, carried out 24 years ago, suggests it’s a hypothesis worth investigating.
The drug halved the rate of Alzheimer’s cognitive decline but was overlooked when the beta-amyloid theory of the disease became dominant, says Ayton. “Perhaps it’s time to refocus the field on looking at iron as a target,” he says.
One easy way of reducing iron levels – having regular blood donations – would not be a good idea for older people as it can bring on anaemia. Also, says Ayton, “there is only a modest correlation between iron levels in the blood and in the brain.”
However, there is an iron-binding drug called deferiprone which gets into the brain and reduces levels of the metal there without disturbing blood levels too much.
Brain iron elevation is implicated in Alzheimer’s disease (AD) pathogenesis, but the impact of iron on disease outcomes has not been previously explored in a longitudinal study. Ferritin is the major iron storage protein of the body; by using cerebrospinal fluid (CSF) levels of ferritin as an index, we explored whether brain iron status impacts longitudinal outcomes in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. We show that baseline CSF ferritin levels were negatively associated with cognitive performance over 7 years in 91 cognitively normal, 144 mild cognitive impairment (MCI) and 67 AD subjects, and predicted MCI conversion to AD. Ferritin was strongly associated with CSF apolipoprotein E levels and was elevated by the Alzheimer’s risk allele, APOE-ε4. These findings reveal that elevated brain iron adversely impacts on AD progression, and introduce brain iron elevation as a possible mechanism for APOE-ε4 being the major genetic risk factor for AD.