Microglial dystrophy in the aged and Alzheimer's disease brain is associated with ferritin immunoreactivity
Abstract
Degeneration of microglial cells may be important for understanding the pathogenesis of aging-related neurodegeneration and neurodegenerative diseases. In this study, we analyzed the morphological characteristics of microglial cells in the nondemented and Alzheimer's disease (AD) human brain using ferritin immunohistochemistry. The central hypothesis was that expression of the iron storage protein ferritin increases the susceptibility of microglia to degeneration, particularly in the aged brain since senescent microglia might become less efficient in maintaining iron homeostasis and free iron can promote oxidative damage. In a primary set of 24 subjects (age range 34-97 years) examined, microglial cells immunoreactive for ferritin were found to constitute a subpopulation of the larger microglial pool labeled with an antibody for HLA-DR antigens. The majority of these ferritin-positive microglia exhibited aberrant morphological (dystrophic) changes in the aged and particularly in the AD brain. No spatial correlation was found between ferritin-positive dystrophic microglia and senile plaques in AD tissues. Analysis of a secondary set of human postmortem brain tissues with a wide range of postmortem intervals (PMI, average 10.94 +/- 5.69 h) showed that the occurrence of microglial dystrophy was independent of PMI and consequently not a product of tissue autolysis. Collectively, these results suggest that microglial involvement in iron storage and metabolism contributes to their degeneration, possibly through increased exposure of the cells to oxidative stress. We conclude that ferritin immunohistochemistry may be a useful method for detecting degenerating microglia in the human brain.
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Two papers found no difference in ferritin cell counts relative to control, and one identified no change in ferritin-associated plaques in one region and a decrease in another.
“whereas two found no difference in cell counts relative to control,33, 51 and one identified no change in ferritin-associated plaques in one region and a decrease in another.100”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [33]
One study that combined counts from the hippocampus with the amygdala, superior frontal gyrus and the superior, middle and inferior temporal gyri found no significant difference relative to control, though a nonsignificant increase was noted.
“whereas one that combined counts from the hippocampus with the amygdala, superior frontal gyrus and the superior, middle and inferior temporal gyri found no significant difference relative to control, though a nonsignificant increase was noted.33”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [33]
Five of the nine studies comparing microglial markers between AD and high pathology control group reported higher levels of microglia markers in AD, three using HLA-DR, one using CD68, and one using both TREM2 and Iba1.
“Five of these studies reported higher levels of microglia markers in AD, three using HLA-DR,7, 33, 40 one using CD68,83 and one using both TREM2 and Iba1.61”
From Markers of microglia in post-mortem brain samples from patients with Alzheimer’s disease: a systematic review (2018) · cites this paper as [33]
Microglial dystrophy has been observed in Alzheimer's brains as well as aged brains.
“Such microglial dystrophy has been observed in Alzheimer's brains as well as aged brains (Lopes et al., 2008).”
From The Role of Iron Regulation in Immunometabolism and Immune-Related Disease (2019) · cites this paper as Lopes et al., 2008
Dystrophic and ferritin-positive microglia might contribute to the pathogenesis of neurodegenerative disorders because of altered microglial function.
“Dystrophic and ferritin-positive microglia might contribute to the pathogenesis of neurodegenerative disorders because of altered microglial function.55”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [55]
Iron phagocytosed by subpopulations of ferritin-positive microglia probably becomes a source of toxic species that cause cellular degeneration.
“Iron phagocytosed by the subpopulations of ferritin-positive microglia cells probably becomes a source of toxic species that cause cellular degeneration.”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [55]
In the elderly brain, there is a subpopulation of ferritin-positive microglia cells and most of these cells have aberrant dystrophic-type morphology.
“In the elderly brain, there is a subpopulation of ferritin-positive microglia cells and most of these cells have aberrant dystrophic-type morphology.”
From The role of iron in brain ageing and neurodegenerative disorders (2014) · cites this paper as [55]
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- Authors
- Lopes, K. O., Sparks, D. L., & Streit, W. J.
- Affiliations
- Banner Sun Health Research Institute (US)
- University of Florida Health (US)
- Corresponding author
- Streit, Wolfgang J.
- ORCID
- Streit, Wolfgang J.
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2008-04-28
- Volume
- 56
- Issue
- 10
- Pages
- 1048-1060
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W2159619745
- Cited by
- 262
- References
- 57
- Citations by year
- 2026: 9 · 2025: 20 · 2024: 22 · 2023: 22 · 2022: 26 · 2021: 23 · 2020: 15 · 2019: 19 · 2018: 12 · 2017: 10 · 2016: 8 · 2015: 14 · 2014: 10 · 2013: 14 · 2012: 8
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG023665, R01AG023211, AG 023665, AG023211)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- ferritin, Alzheimer's disease, brain aging, iron homeostasis, oxidative stress, HLA-DR, amyloid plaques, postmortem interval, human postmortem brain, neurodegeneration
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Female, Ferritins, Humans, Immunohistochemistry, Male, Middle Aged, Microglia
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