It was believed that one of the important causes of the disease were amyloid plaques in the brain tissue. Another key cause is tau, a protein that abnormally aggregates into threadlike tangles inside nerve cells. Now a third factor has emerged.
In a study available online in Neurobiology of Aging, investigators from the Stanford University School of Medicine have identified some iron-containing microglia — specialized inflammatory scavenger cells – in the part of the brain responsible for memory formation, the hippocampus.
According to Michael Zeineh, assistant professor of neuroradiology and the study’s lead author, microglia are the brain’s immune cells. He said they are like watchful police officers keeping a close eye on happenings in the brain. If they notice anything suspicious, they spring into action, engulf the culprits and become angry (inflamed).
However, in people not diagnosed with Alzheimer’s, the post-mortem studies did not show either iron deposits or the engulfing scavenger cells in the hippocampus.
A majority of the iron containing microglia found in the study were in an activated, inflammatory state. Microglia were always seen as potential suspects in the inflammatory pathology of the brain tissue in Alzheimer’s disease. This study confirms that inflamed, iron-associated microglia are present in the hippocampus in Alzheimer’s. The fact that these microglia can me tracked by 7T MRI, could help increase our understanding of the disease.
The researchers noted that this was a preliminary study performed on a small number of human brain specimens.
In a series of steps combining 7T MRI, researchers scanned slabs of brain tissue taken from five Alzheimer’s patients and five control brain specimens. The results showed that four out of the five Alzheimer’s affected brains had black dots in a part of the hippocampus. There were no such shadows in the non-Alzheimer’s brain tissue.
On further probing, the Stanford researchers discovered that iron, frequently engulfed by microglia, was occupying the same spots in the hypothalamus of Alzheimer’s brains where 7T MRI had found black dots. Those microglia were mostly inflamed.
Researchers said there was an absence of amyloid plaques in these spots.
The researchers do not know how the iron gets into brain tissue, or why it accumulates where it does. They speculate, it could be due to micro-injury to small cerebral blood vessels.
The discovery of this new factor does not rule out the role of amyloid plaques in Alzheimer’s disease. The researchers aim to study more wide-ranging areas of the brain and to stain for more cell types within larger numbers of post-mortem brain specimens.
They said they plan to look out for iron-filled microglia in living patients during the early stages of neurodegeneration and memory loss that precedes Alzheimer’s disease.