Alzheimer's disease: Excess iron in brain cells may play key role

Evan Walker
Evan Walker TheMediTary.Com |
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Excessive iron in brain immune cells may be another cause of Alzheimer’s and vascular dementia. Image credit: MichikoDesign/Getty Images.
  • A new study led by researchers from Oregon Health & Science University has uncovered a new mechanism contributing to cognitive decline in Alzheimer’s disease and vascular dementia.
  • The research suggests that ferroptosis, a form of cell death caused by excess iron accumulation, destroys microglia cells, crucial components of the brain’s immune system.
  • This discovery is likely to stimulate interest in the pharmaceutical industry to develop therapeutically important compounds that focus on reducing microglial degeneration in the brain.

A new study, published in Annals of Neurology, found that ferroptosis, a form of cell death triggered by excess iron accumulation inside the cell, leads to the destruction of microglia cells.

These cells play a key role in the brain’s immune function, in Alzheimer’s disease and vascular dementia cases.

The study involved the analysis of brain tissue from deceased dementia patients. It also built on previous work about myelin, which serves as a protective coating for nerve fibers in the brain.

This recent research reveals a chain reaction of neural decay set off by the breakdown of myelin.

The research team found that in patients with Alzheimer’s and vascular dementia, microglia deteriorate in the brain’s white matter.

Microglia are native cells in the brain that typically serve to remove cellular waste as part of the body’s immune response. When myelin is compromised, microglia are activated to clean up the debris.

However, the new research indicates that the microglia themselves are destroyed in the process of eliminating iron-laden myelin, through a type of cell death called ferroptosis.

Considering the extensive research focused on identifying the root causes of dementia in older populations, the researchers point out that it was remarkable that the link to ferroptosis had not been discovered until this study.

The research suggests that the chain reaction of deteriorating microglia seems to be a contributing factor to the worsening cognitive impairment seen in Alzheimer’s disease and vascular dementia.

The initial trigger for this cycle of decline is believed to be frequent instances of reduced blood and oxygen supply to the brain, which could result from acute events like strokes or from chronic conditions such as high blood pressure and diabetes.

Amarish Dave, doctor of osteopathic medicine, a board-certified neurology specialist at Northwestern Medicine not involved in this research, spoke to Medical News Today about the study findings.

He noted that there “were some very interesting potential therapeutic insights to the study.” According to Dave:

“If iron toxicity is responsible for cell death and negative impact, myelin repair targeted therapies of this pathway could impact how we treat Alzheimer’s and vascular dementia. Iron toxicity in the brain is well known and typically from genetic dysfunction. This paper identifies potential iron toxicity from cell death and the debris that accumulates.”

“Our understanding and current treatments for dementia remain largely unchanged for decades. Even newer therapeutic drugs attack old targets, plaques, and tangles,” Dave explained.

“This research opens up the possibility of novel pathophysiologic targets to treat dementia and also enhance recovery if myelin can be repaired,” he added.

Dr. Santosh Kesari, a neurologist at Providence Saint John’s Health Center in Santa Monica, CA, and regional medical director for the Research Clinical Institute of Providence Southern California, also not involved in the research, agreed with this point of view.

“Further work needs to be done,” Dr. Kesari said, “but drugs that target microglial function may be a useful avenue for future therapeutic approaches to prevent neurodegeneration.”

Michael Kentris, DO, an osteopathic physician specializing in neurology at Mercy Health, also not involved in the study, noted that “it is encouraging to see a novel mechanism of degeneration proposed in Alzheimer’s disease and vascular dementia.”

“Given that these are two of the most common types of dementia in general, having a new avenue for investigation is of the utmost importance,” Kentris explained. “Increasing cerebral burden of white matter lesions is associated with an increased risk for dementia and stroke.”

“In current clinical practice, traditional risk factor[s] and lifestyle modifications — e.g. blood pressure control, glucose management, smoking cessation, diet, exercise, etc. — are the most common ways of preventing primary development of white matter lesions. Opening the door for the exploration of new therapeutic targets to reduce the incidence of white matter disease could have the potential to benefit a significant portion of the population.”

– Michael Kentris

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