Iron levels hasten Alzheimer’s disease

Brain

Brain

High levels of iron in the brain could increase the risk of developing Alzheimer’s disease and hasten the cognitive decline that comes with it, new research suggests.

The results of the study, which tracked the brain degeneration of people with Alzheimer’s over a seven-year period, suggest it might be possible to halt the disease with drugs that reduce iron levels in the brain.

 “We think that iron is contributing to the disease progression of Alzheimer’s disease,” neuroscientist Scott Ayton, from the University of Melbourne in Australia, told Anna Salleh at ABC Science.

“This is strong evidence to base a clinical trial on lowering iron content in the brain to see if that would impart a cognitive benefit.”

Alzheimer’s is a devastating disease that researchers suspect “begins when two abnormal protein fragments, known as plaques and tangles, accumulate in the brain and start killing our brain cells,” explains Fiona Macdonald for ScienceAlert.

It starts by destroying the hippocampus – the region of the brain where memories are formed and stored – and eventually damages the region where language is processed, making it difficult for advanced Alzheimer’s patients to communication. As the disease’s gradual takeover continues, people lose the ability to regulate their emotions and behaviour, and to make sense of the world around them.

But previous studies have shown that people with Alzheimer’s disease also have elevated levels of brain iron, which may also be a risk factor for the disease.

“There has been debate for a long period of time whether this is important or whether it’s just a coincidence,” Ayton told ABC Science.

The long-term impact of elevated iron levels on the disease outcome has not been investigated, the researchers say.

So Ayton’s team decided to test this, examining the link between brain iron levels and cognitive decline in three groups of people over seven years. The participants included 91 people with normal cognition, 144 people with mild cognitive impairment, and 67 people with diagnosed Alzheimer’s disease.

At the beginning of the study, the researchers determined the patients’ brain iron levels by measuring the amount of ferritin in the cerebrospinal fluid around the brain. Ferritin is a protein that stores and releases iron.

The researchers did regular tests and MRI scans to track cognitive decline and changes in the brain over the study period.

They found that people with higher levels of ferritin – in all groups – had faster declines in cognitive abilities and accelerated shrinking of the hippocampus. Levels of ferritin were also a linked to a greater likelihood of people with mild cognitive impairment developing Alzheimer’s.

Their data contained some other interesting takeaways: The researchers found higher levels of ferritin corresponded to earlier ages for diagnoses – roughly three months for every 1 nanogram per millilitre increase.

They also found that people with the APOE-e4 gene variant, which is known to be the strongest genetic risk factor for the disease, had the highest levels of iron in their brains.

This suggests that APOE-e4 may be increasing Alzheimer’s disease risk by increasing iron levels in the brain, Ayton told ABC Science.

The researchers say their findings, which were published in the journal Nature Communications, justify the revival of clinical trials to explore drugs to target brain iron levels.

In a study carried out 24 years ago, a drug called deferiprone halved the rate of Alzheimer’s cognitive decline, Ayton told Clare Wilson at NewScientist. “Perhaps it’s time to refocus the field on looking at iron as a target.”

“Lowering CSF ferritin, as might be expected from a drug like deferiprone, could conceivably delay mild cognitive impairment conversion to Alzheimer’s disease by as much as three years,” the team wrote.

Diabetes Associated With Iron Transport

 

Diabetes Cause may be Associated With Iron Transport:

Diabetes Cause may be Associated With Iron Transport

Diabetes Cause may be Associated With Iron Transport

Increased activity of a iron-transport protein destroys insulin-producing beta cells and thereby contributes to diabetes. In addition, the new research shows that mice without this iron transporter are protected against developing diabetes. These results have just been published in the prestigious journal Cell Metabolism. Almost 300,000 Danes have diabetes – 80 per cent have type-2 diabetes, a so-called lifestyle disease. The number of people with diabetes doubles every decade and the disease costs Danish society about DKK 86 million per day. People develop diabetes when the beta cells in their pancreas do not produce enough insulin to meet their body’s needs. New research from the University of Copenhagen and Novo Nordisk A/S links this defect to one particular cellular iron transporter. “Iron is a vital mineral for the healthy functioning of the body and is found in many enzymes and proteins, for example, the red blood pigment that transports oxygen. But iron can also promote the creation of toxic oxygen radicals. An increase in the iron content of the cells may cause tissue damage and disease. We find that increased activity of a certain iron transporter causes damage to the beta cell. And if we completely remove this iron transporter in the beta cells in genetically engineered mice, they are indeed protected against diabetes,” explains Professor Thomas Mandrup-Poulsen, Department of Biomedical Sciences, The Faculty of Health and Medical Sciences. Together with Christina Ellervik, Associate Professor and Professors Børge Nordestgaard and Henrik Birgens from the University of Copenhagen, Thomas Mandrup-Poulsen has previously documented a connection between surplus iron and diabetes risk, based on large population studies. But this is the first time that scientists have found a link between inflammation and iron transport, which appears to be the underlying cause of the observed higher risk. “We need to conduct controlled clinical trials showing that changes in the iron content of the body can reduce the risk of diabetes. Only then will we be able to advise people at risk of diabetes not to take iron supplements, or recommend drug treatment to reduce the amount of iron in the body,” says Thomas Mandrup-Poulsen. The team behind the scientific article in Cell Metabolism can see that the inflammatory signal substances created around the beta cells in both type-1 and type-2 diabetes accelerate the activity of the iron transporter. “The evolutionary explanation of why the highly specialised beta cells are influenced by the inflammatory signal substances and contain the potentially dangerous iron transport proteins is presumably that the short-term increase in the amount of oxygen radicals is critical to the fine-tuning of insulin production during bouts of fever and stress. However, nature had not foreseen the long-term local production of signal substances around the beta cells, which we see in type-1 and type-2 diabetes,” continues Thomas Mandrup-Poulsen. The new results have implications for many scientists, not only those conducting research in diabetes. The beta cell can be used as a model for other cells that are particularly sensitive to iron, such as liver cells and cardiac-muscle cells.