Higher levels of ferritin, an iron storage protein, are associated with reduced cognitive performance and can predict whether a patient suffering from mild cognitive impairment will go on to develop Alzheimer's disease (AD), reports a study published today in Nature Communications.
Elevation of iron levels has previously been seen in the brains of AD patients but a link between brain iron status and clinical outcomes in AD has not been established. Ashley Bush and colleagues examined the association of ferritin levels, detected in the cerebrospinal fluid of 302 people, with various outcomes over seven years. All of these individuals were part of the Alzheimer's Disease Neuroimaging Initiative (ADNI) prospective clinical cohort.
The authors found a negative association between ferritin levels and cognitive performance in cognitively normal participants, participants with mild cognitive impairment, and AD patients. The authors were able to predict the conversion of mild cognitive impairment to AD based on ferritin levels. Ferritin was strongly associated with levels of the AD biomarker apolipoprotein E and was elevated in people carrying the AD risk variant, APOE-ε4.
These studies link the APOE-ε4 variant with brain iron levels and could point to possible mechanisms by which this mutation confers a risk of developing to AD. The study also supports the implementation of therapeutic strategies that lower brain iron to treat AD, but this would need to be explored in future studies.