Scientists at Oregon Health & Science University School of Medicine have made a development that could lead to a greater understanding of Alzheimer’s disease and vascular dementia, a new cause of diseases that affect cognitive performance.
“We missed a key form of cell death in Alzheimer’s disease and vascular dementia,” senior study author Dr. Stephen Buck of Oregon Health & Science University School of Medicine (OHSU) said in a press release. “We haven’t paid much attention to microglia as vulnerable cells, and white matter injury in the brain has received relatively little attention.”
Scientists found that ferroptosis, a type of cell death resulting from the accumulation of iron in cells, destroys a form of cell involved in the brain’s immune response called microglia. This occurs in cases of Alzheimer’s disease and vascular dementia, reports Al-Rai daily.
Essentially, microglia degeneration may be a factor in increasing cognitive decline in patients with Alzheimer’s disease and vascular dementia.
The research paper, in which scientists studied post-mortem human brain tissue from dementia patients, was published in the journal Annals of Neurology.
The team found that microglia degenerate in the white matter of the brain in patients with Alzheimer’s disease and vascular dementia.
Microglia are native brain cells that normally work to remove cellular waste as part of the body’s immune system. Microglia clean up debris when the myelin (or myelin) is damaged. Myelin acts as an insulator and protective covering for nerve fibers in the brain, according to Oregon Health & Science University School of Medicine.
However, scientists have found that microglia are destroyed during the shedding of iron-rich myelin. This destruction occurs through a form of cell death called ferroptosis.
A cascade of microglia degradation events appears to play a role in the progression of cognitive decline in Alzheimer’s disease and vascular dementia, according to Dr. Buck.
Over time, multiple instances of reduced blood flow and oxygen to the brain due to acute strokes or chronic diseases such as high blood pressure and diabetes may contribute to the underlying cause that begins the cycle of cognitive decline, Buck said.
The new study offers a glimmer of hope for scientists, who hope to create improved techniques to slow the dementia process.
Dr. Amaresh Devi, medical director of the Mercyhealth Memory Clinic, who was not involved in the study, said: “If iron toxicity is responsible for cell death and adverse effects, then targeted therapies for myelin repair of this pathway could impact how Alzheimer’s disease and vascular dementia are treated.” Iron toxicity in the brain is well known and is usually caused by a genetic defect. “This paper identifies potential iron toxicity from cell death and debris that accumulates.”
“More work needs to be done, but drugs that target microglia function may be a useful avenue for future therapeutic approaches to prevent neurodegeneration,” said Dr. Santosh Kesari, a neurologist at Providence Saint John’s Health.
Buck indicated in a press statement that he expects pharmaceutical companies to use the results of his study to create compounds aimed at reducing the degeneration of microglia in the brain.
