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Brain's Iron Stores May Be Key to Alzheimer's
  • Posted June 30, 2020

Brain's Iron Stores May Be Key to Alzheimer's

The progression of Alzheimer's disease may accelerate as iron deposits build up in the brain, a new study finds, hinting at a possible role for the mineral in mental decline.

Using MRI scans of 200 older adults with and without Alzheimer's, researchers found that those with the disease generally had higher iron levels in various parts of the brain. And 17 months later, Alzheimer's patients who had had a greater iron accumulation over time also tended to show a faster decline.

Experts stressed that it's not clear whether iron buildup helps cause the worsening symptoms: It may, for instance, just be a sign of overall degeneration in the Alzheimer's-affected brain.

But the findings add to evidence linking iron buildup to declines in thinking and memory.

"Iron levels in the brain are like amyloid and tangles -- a pathological feature that is associated with [Alzheimer's]," explained Dr. Ashley Bush, director of the Melbourne Dementia Research Centre in Australia.

Amyloid "plaques" and neurofibrillary tangles are abnormal protein deposits that build up in the brains of people with Alzheimer's. It's not clear whether they cause the disease.

Bush, who reviewed the new findings, has been studying the potential role of iron accumulation in dementia.

In one study, his team found that among people with amyloid deposits, those with greater iron buildup in the brain had a faster cognitive decline over the next several years. Their performance on tests of memory, language and thinking skills worsened to a greater degree.

According to Bush, there is only one way to prove whether iron accumulation is a cause of dementia symptoms: Clinical trials.

He said he is running a "proof-of-concept" clinical trial to see whether a drug called deferiprone can slow cognitive decline in Alzheimer's patients. Deferiprone is an oral medication that removes excess iron from the body.

For the current study, a team led by Dr. Anna Damulina at the Medical University of Graz in Austria recruited 100 patients with Alzheimer's disease and 100 healthy adults who were the same age.

Using MRI scans, the investigators found that brain iron levels were generally higher in the Alzheimer's group.

When 56 of them had a repeat scan about 17 months later, a pattern emerged: Those with a greater increase in brain iron tended to show worsening performance on standard tests of mental skills.

The findings were published June 30 in the journal Radiology.

What determines a person's brain iron level? Bush said genes are important, as is age. Iron levels typically rise as people get older, even if their brain health is good.

It's not clear why that iron increase is greater in older adults with dementia.

But Bush said his team is studying whether genetic risk factors for Alzheimer's might also boost iron in the brain. They've found that mutations in a gene for amyloid precursor protein seem to do that. A mutation tied to increased Alzheimer's risk can cause brain cells to retain iron, while a mutation linked to decreased risk of the disease helps cells release excess iron.

However, it's too early to call excess iron a culprit in dementia, said Keith Fargo, director of scientific programs and outreach for the nonprofit Alzheimer's Association.

"This study suggests there's some kind of connection between iron accumulation in the brain and cognitive deterioration, but we can't say yet whether the decline causes the iron buildup or the iron buildup causes the decline," he said. "Or maybe there's some other, more complex connection."

Fargo urged people not to make any diet changes based on the findings. "Iron is a critical part of our diet and overall health," he said.

And according to Bush, it's not even clear whether dietary iron speeds up the loading of iron into the brain.

"In theory, it's possible," he said. "But it will take quite a bit of research to determine whether this is a concern that can be modified."

More information

The Alzheimer's Association has an overview of what's known on the causes of Alzheimer's.

SOURCES: Ashley Bush, MD, PhD, director, Melbourne Dementia Research Centre, and professor, psychiatry and neuroscience, University of Melbourne, Australia; Keith Fargo, PhD, director, scientific programs and outreach, Alzheimer's Association, Chicago; Radiology, June 30, 2020
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