Good news! What else have researchers missed? Pardon my facetiousness!
"... "We've missed a major form of cell death in Alzheimer's disease and vascular dementia," ... "We hadn't been giving much attention to microglia as vulnerable cells, and white matter injury in the brain has received relatively little attention." ...
The researchers discovered that the microglia cells themselves are also destroyed as they sweep away the damaged myelin, seemingly by overdosing on iron that is contained within the white matter in significant quantities. ...
The researchers discovered that the microglia cells themselves are also destroyed as they sweep away the damaged myelin, seemingly by overdosing on iron that is contained within the white matter in significant quantities. ...
The cascading effect of microglia death and white matter degeneration appears to play a part in the cognitive decline linked to Alzheimer's and vascular dementia, according to the new study ..."
"... A new study, ... reveals for the first time that a form of cell death known as ferroptosis — caused by a buildup of iron in cells — destroys microglia cells, a type of cell involved in the brain’s immune response, in cases of Alzheimer’s and vascular dementia. ...
The researchers discovered that microglia degenerates in the white matter of the brain of patients with Alzheimer’s and vascular dementia. ...
When myelin is damaged, microglia swarm in to clear the debris. In the new study, researchers found that microglia themselves are destroyed by the act of clearing iron-rich myelin — a form of cell death known as ferroptosis. ..."
When myelin is damaged, microglia swarm in to clear the debris. In the new study, researchers found that microglia themselves are destroyed by the act of clearing iron-rich myelin — a form of cell death known as ferroptosis. ..."
From the abstract:
"Objective
Because the role of white matter (WM) degenerating microglia (DM) in remyelination failure is unclear, we sought to define the core features of this novel population of aging human microglia.
Methods
We analyzed postmortem human brain tissue to define a population of DM in aging WM lesions. We used immunofluorescence staining and gene expression analysis to investigate molecular mechanisms related to the degeneration of DM.
Results
We found that DM, which accumulated myelin debris were selectively enriched in the iron-binding protein light chain ferritin, and accumulated PLIN2-labeled lipid droplets. DM displayed lipid peroxidation injury and enhanced expression for TOM20, a mitochondrial translocase, and a sensor of oxidative stress. DM also displayed enhanced expression of the DNA fragmentation marker phospho-histone H2A.X. We identified a unique set of ferroptosis-related genes involving iron-mediated lipid dysmetabolism and oxidative stress that were preferentially expressed in WM injury relative to gray matter neurodegeneration.
Interpretation
Ferroptosis appears to be a major mechanism of WM injury in Alzheimer's disease and vascular dementia. WM DM are a novel therapeutic target to potentially reduce the impact of WM injury and myelin loss on the progression of cognitive impairment."
OHSU scientists discover new cause of Alzheimer’s, vascular dementia (primary source) Study highlights microglia degeneration in brain caused by iron toxicity
Figure 7 Summary of data supporting a role for ferroptosis in microglial degeneration in human WMI related to vascular dementia or AD.
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