OHSU Scientists Identify Ferroptosis of Microglia as Novel Mechanism in Alzheimer’s and Vascular Dementia

ByOregon Health & Science University（Oregon Health & Science University，OHSU) A new study led by scientists was published online in the journal "Annals of Neurology》（Annals of Neurology) above,Revealed for the first time that in the cases of Alzheimer's disease and vascular dementia, a process known as ferroptosis（Ferroptosis）Form of cell death(Caused by the accumulation of iron in cells)Destroyed microglia，Microglia are cells involved in immune responses in the brain.。

ResearchersResearch on Brain Tissue of Dementia Patients After Death。

“This is a significant discovery., "Senior AuthorStephen BackDr. said, he isOHSU School of MedicineNeuroscientist and Professor of Pediatrics.

Back Has been studying for a long timeMyelin(Myelin), a protective sheath similar to insulation that covers nerve fibers in the brain, including delays in myelination formation in preterm infants. New researchExtended this work by revealing a cascade form of neurodegeneration triggered by myelin degeneration.. They utilized the main author of the study, a postdoctoral researcher in the Back laboratory Philip Adeniyi A new technology developed by a doctor made this discovery.

Stephen Back, MD, PhD, Professor of Neurosciences and Pediatrics at The Ohio State University College of Medicine (left), and Dr. Philip Adeniyi, Postdoctoral Researcher in the Back Lab

Researchers have found,Patients with Alzheimer's disease and vascular dementia experience degeneration of microglia in the white matter of the brain.。

MicrogliaAre cells that reside in the brain, typicallyParticipate in the clearance of cellular debris as part of the human immune system。When myelin is damaged, microglia swarm to clear the debris.. In this new study,Microglia themselves can be damaged by clearing iron-rich myelin., which is calledFerroptosis（Ferroptosis）Form of cell death。

Given the scientific community's intense interest in the potential causes of Alzheimer’s disease, Back said,Researchers have only now linked it to ferroptosis., which is surprising.

Back said, "WeOverlooked the primary form of cell death in Alzheimer's disease and vascular dementia. WeMicroglia have not been considered as vulnerable cells, and white matter damage in the brain has received little attention.。”

Back, co-author of the study, M.D.Kiera Degener-O’Brien initially discovered the degeneration of microglia in tissue samples.。Adeniyi subsequently developed a new immunofluorescence technique to determine iron toxicity-induced microglial degeneration in the brain.Back said, thisPossibly because myelin debris itself is rich in iron。

In fact,Immune Cells Die in the Line of Duty。

"Everyone knowsMicroglia are activated to mediate inflammation," Back said, "butNo one knew that so many of their cells would die.. Surprisingly, weIt is only now that this realization has dawned.。”

Back said that the study found,The cascade effect of transformed microglia appears to be a mechanism behind cognitive decline in patients with Alzheimer’s disease and vascular dementia.. He expects pharmaceutical companies to leverage this new discovery for developmentCompounds Focused on Reducing Microglial Degeneration in the Brain。

"This is the next direction for development in this field," he said, "discoveries like ours.Stimulate the pharmaceutical industry to develop compounds with significant therapeutic effects。”

He said,The potential causes of triggering recession cycles may be related to repeated episodes of low blood flow and low oxygen delivery to the brain caused by acute stroke or chronic diseases such as hypertension and diabetes.。

Back said: "Dementia is a process that lasts for many years. We must address this issue from the very beginning so that it does not spiral out of control.。”

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