The Role of Iron Overload in Alzheimer’s Disease

In my video on whether aluminum plays a role in the development of Alzheimer’s disease I noted that most scientists give little or no credence to this theory, but if aluminum doesn’t cause Alzheimer’s disease, then why does the metal chelator drug deferoxamine help? A study published more than thirty years ago is one of the few clinical trials ever to suggest a change in the course of Alzheimer’s disease. 48 patients thought to have Alzheimer’s were randomized to receive injections twice a day, five days a week of the deferoxamine, given an oral placebo, or no treatment at all for two years. The rate of cognitive deterioration in the control groups was twice as rapid compared to the deferoxamine group. Ideally, the placebo would have been injected as well, but given the number of injections required, an ethics review committee wouldn’t allow it. That’s why there was a third no-treatment group, to assess for placebo effects. Yes, injected placebos can be more powerful than swallowed placebos, but no difference was found between the placebo ill group and the do-nothing group, suggesting no placebo effect at all under the circumstances.

The researchers attributed this slowing in half of cognitive decline to the ability of the drug to bind aluminum, but deferoxamine was actually designed as an iron chelator. Deferoxamine’s affinity for iron is six times greater than for aluminum, and iron is a thousand times more abundant in the brain. Might the dramatic effects be due to ridding the brain of excess iron?

Rats fed high iron diets develop Alzheimer’s-like brain pathology that can be mediated by an iron chelator and/or antioxidants, suggesting the pro-oxidant effect of excess iron may play a role in neurodegenerative changes. A series of heavily cited studies out of one laboratory found higher overall iron levels in a certain area of the brain, but seven other labs failed to replicate these findings. More recently, however, visualization techniques offering greater spatial resolution show that iron does seem to co-localize to Alzheimer’s plaques, revealing potentially a big role for iron in Alzheimer’s disease. Iron only appears to accelerate plaques in people with pre-existing amyloid buildup, though, so excess iron may just hasten the disease rather than initiate it.

I was surprised to learn the decades old deferoxamine study was never replicated. There are, however, new orally-active brain-penetrating iron chelators and a new clinical trial underway to see if it can delay dementia in those with mild cognitive impairment. As soon as the results are released, I’ll do a video about it here, on NutritionFacts.org.