Activated iron-containing microglia in the human hippocampus identified by MRI

[Bob]

This came to my attention via Kathryn Stephens on Twitter.

They think they have detected an increased amount of activated microglia in the hippocampus of Alzheimer’s patients (but, interestingly, not consistently in the same place as amyloid plaques or Tau proteins.)

They hypothesise: "Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI."

Iron-containing inflammatory cells seen in Alzheimer's brains
Stanford University Medical Center
July 20, 2015

http://med.stanford.edu/news/all-ne...ammatory-cells-seen-in-alzheimers-brains.html

Using high-field MRI technology and staining techniques, scientists have located inflamed, iron-containing scavenger cells in a memory-formation structure in the brains of Alzheimer’s patients who died.

Examining postmortem tissue from the brains of people with Alzheimer’s disease, Stanford University School of Medicine investigators identified what appear to be iron-containing microglia — specialized scavenger cells that sometimes become inflammatory — in a particular part of the hippocampus, a key brain structure whose integrity is critical to memory formation.

In post-mortem brain tissue from people not diagnosed with Alzheimer’s, neither the iron deposits nor the scavenger cells engulfing them were present in that brain region.

The findings, recounted in a study now available online in Neurobiology of Aging, suggest that high-field magnetic resonance imaging, in particular an advanced version called 7T MRI that uses a powerful 7-Tesla magnet, could someday be used to diagnose and monitor Alzheimer’s patients earlier than is currently possible.

The findings also add a new suspect to the Alzheimer’s disease lineup. A long-held hypothesis holds that the most notorious feature of Alzheimer’s disease, amyloid plaques, is the main cause of the disorder. These plaques are extracellular aggregations of a small protein called beta-amyloid that are prominent in diseased patients’ brains, as well as in mouse models of the disease. The other most cited key player is tau, another Alzheimer’s-associated protein that abnormally aggregates into threadlike tangles inside nerve cells. Surprisingly, in the brain region of interest there was no consistent overlap between the iron-laden microglia and the amyloid plaques or tau.

“Microglia are the brain’s immune cells,” said Michael Zeineh, MD, PhD, assistant professor of neuroradiology and the study’s lead author. In their resting state, they’re like police officers in the doughnut shop, sitting down and relaxing, their guns holstered, but keeping their eyes open while placidly munching on whatever cellular debris or stray substances might come their way. If they encounter anything suspicious, though, they whirl into action. Activated microglia are like officers with their guns out and firing, Zeineh said.

Continue reading here:
http://med.stanford.edu/news/all-ne...ammatory-cells-seen-in-alzheimers-brains.html

 

[Bob]

This is the research paper.

Activated iron-containing microglia in the human hippocampus identified by magnetic resonance imaging in Alzheimer disease.
Michael M. Zeineh, Yuanxin Chen, Hagen H. Kitzler, Robert Hammond, Hannes Vogel, Brian K. Rutt.
Neurobiology of Aging. 2015.
DOI: 10.1016/j.neurobiolaging.2015.05.022
http://www.neurobiologyofaging.org/article/S0197-4580(15)00306-1/abstract

Abstract
Although amyloid plaques and neurofibrillary pathology play important roles in Alzheimer disease (AD), our understanding of AD is incomplete, and the contribution of microglia and iron to neurodegeneration is unknown. High-field magnetic resonance imaging (MRI) is exquisitely sensitive to microscopic iron. To explore iron-associated neuroinflammatory AD pathology, we studied AD and control human brain specimens by (1) performing ultra-high resolution ex vivo 7 Tesla MRI, (2) coregistering the MRI with successive histologic staining for iron, microglia, amyloid beta, and tau, and (3) quantifying the relationship between magnetic resonance signal intensity and histological staining. In AD, we identified numerous small MR hypointensities primarily within the subiculum that were best explained by the combination of microscopic iron and activated microglia (p = 0.025), in contradistinction to the relatively lesser contribution of tau or amyloid. Neuropathologically, this suggests that microglial-mediated neurodegeneration may occur in the hippocampal formation in AD and is detectable by ultra-high resolution MRI.

 

[Sidereal]

Wasn't he the first author on the CFS DTI study out of Stanford recently?