Link between high brain iron levels and Alzheimer's

New research by CSIRO and the Florey Institute of Neuroscience and Mental Health has shown an association between higher levels of brain iron, the presence of Alzheimer’s protein amyloid, and poorer memory and language skills.

Led by Dr Scott Ayton and Professor Ashley Bush from the Florey Institute, the study has been published in the journal Brain. 

Scientists have long known that the slow build-up of a substance known as amyloid in the brain determines whether people will eventually experience Alzheimer’s disease. The team of Australian researchers have shown that about 30% of people in their 70s have high levels of amyloid in their brain — but confusingly, some retain all their cognitive faculties much longer than others. Some other factor had to be involved. It turns out, that something else may be iron.

The study used the data gathered from 117 participants in the Australian Imaging, Biomarker & Lifestyle Flagship Study of Ageing (AIBL). Six years ago, 117 AIBL participants had their levels of amyloid protein and brain iron measured using brain scans — PET for amyloid and MRI for iron. Every 18 months since, their memory, language, attention and executive functioning has been exhaustively tested. The researchers used this data to see whether brain iron and amyloid can predict people’s cognitive performance.

“Cognitive abilities like short-term memory, executive function and language ability declined much faster in people with high brain iron levels and high amyloid levels, even if they were otherwise healthy, than those with low brain iron who were also amyloid positive,” said Dr Ayton.

Although this study used correlations between iron, amyloid and cognitive performance, and thus iron can’t yet be called a ‘causative’ agent in Alzheimer’s disease, the results make compelling biological sense.

“These results suggest that iron acts together with amyloid to speed up the Alzheimer’s disease process. Those individuals with high amyloid but low iron will also eventually go on to develop Alzheimer’s disease, but much later than their high-iron counterparts,” said Dr Ayton.

The research used technology developed by CSIRO and was conducted in a collaborative study funded by the CRC for Mental Health. “We’ve refined MRI technology to allow the very precise mapping of iron levels in the brain,” said CSIRO researcher Dr Olivier Salvado, one of the lead authors of the paper.

“Collaborating with world-leading scientists at the Florey Institute was critical to drive our innovation into potential clinical use.”

The researchers are excited by the study, because it opens up a promising new avenue for Alzheimer’s drug treatments. To test the theory, Florey scientists plan to use an existing drug, deferiprone, to ‘mop up’ excess iron in the brain and see if it can slow down the progression of the disease.

“The 3D trial is extremely exciting, because for the first time we will able to assess someone’s risk of progressing into cognitive decline without needing to perform invasive and costly tests. We will also be testing a compound that may prevent or slow the natural course of the disease,” said Professor Bush.

“If the 3D trial results prove that low iron slows disease progression, we imagine a future where your GP sends you off for your 60-year health check, including a brain iron MRI scan, which is quick, cheap and painless. If you have high brain iron, then we would order an amyloid PET scan. Once we had those two measurements, we could predict the likely onset of Alzheimer’s and begin you on therapy to lower the iron and delay disease onset.”