New research reveals cell death contributing to Alzheimer’s and vascular dementia

PORTLAND, Ore. — Researchers at Oregon Health & Science University said in a study they have discovered a new way a type of cell important for brain health is dying in the brains of people with Alzheimer’s disease and vascular dementia, and its death contributes to ongoing dementia.

Dr. Stephen Back, a neuroscientist and professor of pediatrics in the OHSU School of Medicine and senior author of the study published online in the journal “Annals of Neurology” in late August, called it a major finding and said it may help pharmaceutical companies develop drugs that will target and block the death of the cell.

The type of cell death the researchers said was occurring was ferroptosis, which happens when iron builds up in cells. In their study, the researchers said the cells that were killed off by iron toxicity were microglia, which are important in regulating brain inflammation.

Back and his colleagues dissected 40 human brains from people who died suffering from some kind of dementia. From the tissue samples, they said they discovered microglia that were abnormal and showed signs of dying, triggered by iron toxicity.

In an interview earlier this month, Back described microglia like little Pac-Mans, going around in the brain and cleaning up cellular debris — like fragments from what are known as myelin sheaths, which are rich in iron. Iron, while important for body and brain function, is toxic if not bound to a protein.

“What happens when the myelin breaks down, these cells, the microglia, start to chew up that myelin, they encounter the iron in a form that’s no longer bound to the protein,” Back said.

Myelin is important in the transmission of electrical signals throughout the body. It provides insulation for nerve fibers. By doing so, it allows those signals to travel through the brain and body quickly.

However, Pam Maher, a research professor of cellular neurobiology at the Salk Institute for Biological Studies in La Jolla, California, just north of San Diego, said the evidence out there linking this type of cell death to Alzheimer’s disease and dementia is circumstantial and there are studies that conflict with each other on how susceptible microglia is to iron toxicity. She was not involved in the OHSU study.

“There’s evidence that there are changes in the brain during aging, more so in Alzheimer’s disease, that are consistent with the activation of this pathway, … but there are some inconsistencies, in that particularly during the early stages of Alzheimer’s disease there’s not a lot of cell death, at least there’s not a lot of death in neurons,” she said. “So it may be playing a role, but maybe not as a death pathway, as sort of a chronic injury pathway.”

Maher said more evidence will be needed to better link this process of iron toxicity to microglia death. She said the OHSU researchers only looked at a few markers of this type of cell death and would need to look at more markers to strengthen their case.

Furthermore, she said the markers the OHSU researchers did look at weren’t necessarily specific to this type of cell death and several “classical markers” were not changed in the microglia.

But she said the research was unique because it examined a part of the brain not usually studied in Alzheimer’s disease research.

Most of the studies look at the part of the brain called gray matter and have linked Alzheimer’s disease to the accumulation of proteins beta amyloid and tau, contributing to the death of nerve cells responsible for learning, memory, emotions and higher thinking.

OHSU’s study, however, focused on the degeneration and death of microglia in a portion of the brain called white matter.

“Most of our brain is actually made up of white matter,” Back said. “And surprisingly, most scientists focus most of their attention on the gray matter because they think that’s the most interesting part, but, in fact, white matter is where so much of the injury happens to the brain.”

Back also said that blood flow to the brain is important for the health of the organ, but as we age, blood flow can be disrupted because of the narrowing of arteries, hypertension, diabetes and strokes. He stressed that diet and controlling blood pressure are important factors in keeping blood flowing properly to the brain.

A projected 6.93 million people 65 years and older will live with Alzheimer’s disease next year in the United States, according to the Alzheimer’s Association.

The disease is progressive and eventually fatal. In addition to having memories robbed, those with the disease can have changes in mood and problems performing everyday tasks. Eventually, they’ll need help in every facet of life. There is no known cure.