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Trial Could Point the Way to Halt Alzheimer’s Disease

A collaboration between the Florey Institute and CSIRO has found an association between higher levels of brain iron, the presence of amyloid protein and poorer memory and language skills.

Scientists have long known that the slow build-up of amyloid in the brain determines whether people will eventually experience Alzheimer’s disease. About 30% of people in their seventies have high levels of amyloid in their brain, yet some retain all their cognitive faculties much longer than others.

Some other factor had to be involved. That something else may be iron.

Six years ago, brain scans of 117 participants in the Australian Imaging and Biomarker Lifestyle study measured their levels of amyloid and brain 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. The results have now been published in Brain.

“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 Scott Ayton of the Florey Institute.

Higher iron levels in the hippocampus of amyloid-positive people predicted worse performance on a series of short-term memory tasks. The hippocampus is where our short-term memories are created and stored.

Similarly, our powers of language are mainly centred in the temporal and frontal lobes, and higher iron in these brain regions predicted poorer performance in language-based tasks.

“These results suggest that iron acts together with amyloid to speed up the Alzheimer’s disease process,” Ayton says. “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.”

The study opens up a promising new avenue for Alzheimer’s drug treatments. Florey scientists now 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,” says Prof Ashley Bush of the Florey Institute. “We will also be testing a compound that may prevent or slow the natural course of the disease.

“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.”

If you are over 65 and noticed that your memory is declining, or you are newly diagnosed with dementia, you can register your interest in being involved in the study at