High resolution dissection of reactive glial nets in Alzheimer’s disease
Open accessAbstract
Fixed human brain samples in tissue repositories hold great potential for unlocking complexities of the brain and its alteration with disease. However, current methodology for simultaneously resolving complex three-dimensional (3D) cellular anatomy and organization, as well as, intricate details of human brain cells in tissue has been limited due to weak labeling characteristics of the tissue and high background levels. To expose the potential of these samples, we developed a method to overcome these major limitations. This approach offers an unprecedented view of cytoarchitecture and subcellular detail of human brain cells, from cellular networks to individual synapses. Applying the method to AD samples, we expose complex features of microglial cells and astrocytes in the disease. Through this methodology, we show that these cells form specialized 3D structures in AD that we refer to as reactive glial nets (RGNs). RGNs are areas of concentrated neuronal injury, inflammation, and tauopathy and display unique features around β-amyloid plaque types. RGNs have conserved properties in an AD mouse model and display a developmental pattern coinciding with the progressive accumulation of neuropathology. The method provided here will help reveal novel features of the healthy and diseased human brain, and aid experimental design in translational brain research.
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Reactive astrocytes and microglia closely interact with one another and with Aβ, forming peri-plaque glial nets.
“Reactive astrocytes and microglia closely interact with one another and with Aβ, forming peri-plaque glial nets9.”
From Regulation of cell distancing in peri-plaque glial nets by Plexin-B1 affects glial activation and amyloid compaction in Alzheimer’s disease (2024) · cites this paper as [9]
Microglia activation is observed in various neurodegenerative diseases.
“Microglia activation is observed in various neurodegenerative diseases.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [12]
Reactive microglia are clustered near Aβ plaques in various brain regions of AD mice and human postmortems.
“These reactive microglia were found to be clustered near Aβ plaques in various brain regions of AD mice and human postmortems.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [12]
In AD brains, microglia surrounding amyloid plaques have activated amoeboid morphology with enlarged soma and retracted processes.
“In AD brains, microglia surrounding amyloid plaques display activated amoeboid morphologies with enlarged soma and retracted processes, indicating microglial response to protein accumulation or increased inflammatory mediators [41, 46-48].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [47]
This morphology indicates microglial response to protein accumulation or increased inflammatory mediators.
“indicating microglial response to protein accumulation or increased inflammatory mediators [41, 46-48].”
From Transcriptional and Epigenetic Regulation of Microglia in Health and Disease (2019) · cites this paper as [47]
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References 61 · Cited by 111
- Authors
- Bouvier, D. S., Jones, E. V., Quesseveur, G., Davoli, M. A., A. Ferreira, T., Quirion, R., Mechawar, N., & Murai, K. K.
- Affiliations
- Montreal General Hospital (CA)
- Douglas Mental Health University Institute (CA)
- Corresponding author
- Murai, Keith K.
- Venue
- Scientific Reports
- Published
- 2016-04-19
- Volume
- 6
- Issue
- 1
- Pages
- 24544-24544
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC4835751
- OpenAlex
- W2338312595
- Cited by
- 111
- References
- 61
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 10 · 2023: 15 · 2022: 23 · 2021: 9 · 2020: 5 · 2019: 9 · 2018: 6 · 2017: 6 · 2016: 1
- FWCI
- 5.90
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Pfizer
- Fondation Brain Canada
- Canada Research Chairs
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- Alzheimer's disease, microglia, astrocytes, human brain tissue, synapses, tauopathy, amyloid plaques, neuropathology, mouse models of Alzheimer's disease
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Animals, Astrocytes, Brain, Diagnosis, Disease Models, Animal, Female, Humans, Male, Neuroglia, Neurons, Synapses, Microglia, Mice, Plaque, Amyloid
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