Association between Alzheimer’s and high brain iron to be tested in new clinical trial
A new study published in the journal Molecular Psychiatry is suggesting high iron levels in the brain may fundamentally trigger the progressive neurodegeneration associated with dementia and Alzheimer's disease. A clinical trial is now underway exploring whether Alzheimer's-related cognitive decline can be slowed by lowering brain iron levels.
Alzheimer's research is currently in a strange phase, after a continuing run of failed clinical drug trials, many researchers are questioning whether the longstanding amyloid hypothesis is correct. Although every patient suffering from Alzheimer's disease has been found to harbor high levels of amyloid proteins in their brain, not every person with high levels of those toxic proteins ultimately go on to develop Alzheimer's disease. In fact some studies have revealed up to 30 percent of cognitively healthy senior citizens can display high levels of amyloid proteins in their brain without developing Alzheimer's disease.
This observation suggests some other factor may be involved in triggering the neurodegeneration associated with higher amyloid accumulations in the brain.
To investigate what this additional factor might be, the new study examined brain samples from over 200 donors, recruited when they were alive, and cognitively tracked for up to 12 years before death.
The results revealed a strong correlation between elevated brain iron levels, severe cognitive decline, and high accumulations of amyloid proteins. Interestingly cognitive decline was only seen in subjects with both high amyloid accumulations and high iron levels. Those subjects with high amyloid accumulation in the absence of high brain iron levels did not seem to suffer from the same cognitive decline.
The huge question hovering over this research is of course that of causation. The researchers fairly note there is no evidence to clearly suggest high brain iron levels actually cause the cognitive decline associated with Alzheimer's. It may just as well be a consequence of the neurodegenerative process. However the study does suggest, at the very least, iron accumulation may offer a secondary propulsion mechanism, accelerating cognitive decline. It has been previously established that iron accumulation in the brain can induce oxidative damage and enhance cell death.
"Our data do not prove that iron causes disease progression in Alzheimer's disease, but the strong association we discovered invites the possibility that iron is a big contributing factor to cognitive decline in Alzheimer's disease," says Scott Ayton, a researcher working on the new study from the Florey Institute of Neuroscience and Mental Health in Melbourne.
An important factor the researchers stress should be noted is that the brain iron levels recorded in these studies have no relationship with dietary iron levels. Brain iron levels are modulated by separate chemical processes occurring in the brain, so oral iron supplements or specific dietary interventions are most likely irrelevant in regards to this mechanism.
In order to explore the link between iron and Alzheimer's the researchers are currently undertaking a phase 2 clinical trial to find out if reducing brain iron levels can slow the progression of the disease. The clinical trial will use an already approved drug called deferiprone, which was initially developed to treat conditions of iron overload in the blood. Deferiprone has been found to be able to cross the blood-brain barrier so it is hypothesized to potentially be effective in lowering brain iron levels.
The new study was published in the journal Molecular Psychiatry.