High Brain Iron Hastens Alzheimer's Disease

High ferritin levels in the cerebrospinal fluid (CSF) could increase the risk of developing Alzheimer's disease (AD) and accelerate the cognitive decline that comes with it, according to a new study.

Researchers at the University of Melbourne (Australia), Cornell University (Ithaca, NY, USA), and other partners of the Alzheimer’s Disease Neuroimaging Initiative (ADNI; La Jolla, CA, USA) conducted a study to examine the possible link between brain iron levels and cognitive decline in three groups over seven years. Participants included 91 people with normal cognition, 144 people with mild cognitive impairment, and 67 people with diagnosed AD.

The researchers first determined participants’ brain iron levels by measuring the amount of ferritin in the CSF, which surrounds the brain. They continued to perform regular tests and magnetic resonance imaging (MRI) scans to track cognitive decline and changes in the brain over the study period. The results showed that people with higher levels of ferritin (in all groups) suffered 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 AD.

The researchers also found that higher levels of ferritin corresponded to earlier ages for diagnoses of AD, roughly three months for every 1 nanogram per milliliter increase. Another finding was that the ferritin was strongly associated with CSF apolipoprotein E (APOE-e4) levels, and that those participants with the AD risk allele, APOE-ɛ4, a gene variant which is known to be the strongest genetic risk factor for the disease, had the highest levels of iron in their brains. The study was published on May 19, 2015, in Nature Communications.

“We think that iron is contributing to the disease progression of Alzheimer's disease; 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,” said lead author neuroscientist Scott Ayton, PhD, of the University of Melbourne. “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. Perhaps it's time to refocus the field on looking at iron as a target.”

AD, named after Dr. Alois Alzheimer, who first described it, is a physical disease that is the result of protein buildup in the brain, forming structures called plaques and tangles. These lead to the loss of connections between nerve cells, and eventually to their death and loss of brain tissue. As AD progresses, memory loss, communication, reasoning, and orientation become increasingly severe, and sufferers need more and more day-to-day support from those who care for them. AD affects almost 50% of those over the age of 85, and is the sixth leading cause of death in the US.

Related Links:
University of Melbourne
Cornell University