ArticleJournal of neuroinflammation2022
Ultrastructural characterization of dark microglia during aging in a mouse model of Alzheimer's disease pathology and in human post-mortem brain samples.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 74 citations in OpenAlex.
- Glial cells in neuropathic pain.Physiological reviews · 2026Review
- IL-33/ST2 Signaling and Microglial Functional-State Transitions After Spinal Cord Injury: Direct Evidence and Mechanistic Hypotheses.International journal of molecular sciences · 2026Review
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- Histone Deacetylase Inhibitor Combined with Rosiglitazone Improves Cognitive Function Via Microglial Polarization and Increased Mature/Pro-BDNF in Alzheimer's Disease.Advanced pharmaceutical bulletin · 2026Article
- Microglial response to sleep deprivation depends on the hippocampal region and paradigm used in adult male mice.Brain, behavior, & immunity - health · 2026Article
- Digging Deep into Alzheimer Disease: How Electron Microscopy Helps Elucidating Its Pathogenesis.Cellular and molecular neurobiology · 2026Review
- Caveolin-1 Regulates Ultrastructural Alterations of Astrocytes in Chronic Cerebral Hypoperfusion.Inflammation · 2025Article
- Targeting Microglial Activation to Modulate Neuroinflammation in Alzheimer's Disease.Neuromolecular medicine · 2025Review
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- Microglia-Mediated Phagocytosis in Alzheimer's Disease: Mechanisms, Heterogeneity, and Therapeutic Insights.Biomolecules · 2025Review
- Microglial glycolytic reprogramming in alzheimer's disease: association with impaired phagocytic function and altered vascular proximity.Journal of neuroinflammation · 2025Article
- Harnessing human iPSC-microglia for CNS-wide delivery of disease-modifying proteins.Cell stem cell · 2025Article
- Exploring Iron Deposition Patterns Using Light and Electron Microscopy in the Mouse Brain Across Aging and Alzheimer's Disease Pathology Conditions.Journal of neurochemistry · 2025Article
- The Hallmarks of Ageing in Microglia.Cellular and molecular neurobiology · 2025Review
- Multiple sclerosis: what have we learned and can we still learn from electron microscopy.Cellular and molecular life sciences : CMLS · 2025Review
- Decoding microglial immunometabolism: a new frontier in Alzheimer's disease research.Molecular neurodegeneration · 2025Review
- A neurodegenerative cellular stress response linked to dark microglia and toxic lipid secretion.Neuron · 2025Article
- Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus.Journal of neuroinflammation · 2025Article
- Fundamental Neurochemistry Review: Lipids across microglial states.Journal of neurochemistry · 2025Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A diverse heterogeneity of microglial cells was previously described in Alzheimer's disease (AD) pathology, including dark microglia, a state characterized by ultrastructural markers of cellular stress. To provide novel insights into the roles of dark microglia during aging in the context of AD pathology, we performed a quantitative density and ultrastructural analysis of these cells using high-throughput scanning electron microscopy in the ventral hippocampus CA1 stratum lacunosum-moleculare of 20-month-old APP-PS1 vs C57BL/6J male mice. The density of dark microglia was significantly higher in APP-PS1 vs C57BL/6J mice, with these cells accounting for nearly half of all microglia observed near amyloid-beta (Aβ) plaques. This dark microglial state interacted more with dystrophic neurites compared to other APP-PS1 microglia and possessed glycogen granules, associated with a metabolic shift toward glycolysis, which provides the first ultrastructural evidence of their presence in microglia. Dark microglia were further observed in aging human post-mortem brain samples showing similar ultrastructural features as in mouse. Overall, our results provide a quantitative ultrastructural characterization of a microglial state associated with cellular stress (i.e., dark microglia) that is primarily restricted near Aβ plaques and dystrophic neurites. The presence of this microglial state in the aging human post-mortem brain is further revealed.
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