Isolation of glia from Alzheimer’s mice reveals inflammation and dysfunction
Abstract
Reactive astrocytes and microglia are associated with amyloid plaques in Alzheimer's disease (AD). Yet, not much is known about the molecular alterations underlying this reactive phenotype. To get an insight into the molecular changes underlying AD induced astrocyte and microglia reactivity, we performed a transcriptional analysis on acutely isolated astrocytes and microglia from the cortex of aged controls and APPswe/PS1dE9 AD mice. As expected, both cell types acquired a proinflammatory phenotype, which confirms the validity of our approach. Interestingly, we observed that the immune alteration in astrocytes was relatively more pronounced than in microglia. Concurrently, our data reveal that astrocytes display a reduced expression of neuronal support genes and genes involved in neuronal communication. The microglia showed a reduced expression of phagocytosis and/or endocytosis genes. Co-expression analysis of a human AD expression data set and the astrocyte and microglia data sets revealed that the inflammatory changes in astrocytes were remarkably comparable in mouse and human AD, whereas the microglia changes showed less similarity. Based on these findings we argue that chronically proinflammatory astrocyte and microglia phenotypes, showing a reduction of genes involved in neuronal support and neuronal signaling, are likely to contribute to the neuronal dysfunction and cognitive decline in AD.
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Plaque-associated microglia exhibit morphological and molecular differences compared to non-plaque-associated cells in AD.
“Plaque-associated microglia exhibit morphological and molecular differences compared to non-plaque-associated cells in AD44,45,46.”
From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [46]
Transcriptomic profiling shows that reactive astrocytes adopt distinct molecular states in different disease models, in different CNS regions, and in brain tumors.
“Such transcriptomic profiling specifically shows that reactive astrocytes adopt distinct molecular states in different disease models48,66–70, in different CNS regions70, and in brain tumors71.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [67]
Reactive astrocytes are diverse, as demonstrated by transcriptomic profiling of mouse bulk astrocytes or preselected astrocyte populations.
“Likewise, reactive astrocytes are also diverse, as unequivocally demonstrated by microarray-based66–68 and RNAseq-based48,69–71 transcriptomic profiling of mouse bulk astrocytes48,66–70 or of astrocyte populations preselected according to cell-surface markers71.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [67]
mRNA profiles of microglia sorted by flow cytometry from the brains of β-amyloid mouse models show marked changes in expression of hundreds of genes.
“mRNA profiles of microglia sorted by flow cytometry from the brains of β-amyloid mouse models show marked changes in expression of hundreds of genes (Orre et al., 2014; Wang et al., 2015; Srinivasan et al., 2016; Keren-Shaul et al., 2017).”
From Microglia in Alzheimer’s disease (2018) · cites this paper as Orre et al., 2014
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- Authors
- Orre, M., Kamphuis, W., Osborn, L. M., Jansen, A. H. P., Kooijman, L., Bossers, K., & Hol, E. M.
- Affiliations
- Netherlands Institute for Neuroscience (NL)
- Corresponding author
- Hol, Elly M.
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 35
- Issue
- 12
- Pages
- 2746-2760
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W2010683624
- Cited by
- 394
- References
- 55
- Citations by year
- 2026: 8 · 2025: 25 · 2024: 26 · 2023: 41 · 2022: 41 · 2021: 49 · 2020: 37 · 2019: 30 · 2018: 35 · 2017: 36 · 2016: 33 · 2015: 28 · 2014: 3
- FWCI
- 17.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- KNAW research portal (Royal Academy of Art and Sciences (KNAW)) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Internationale Stichting Alzheimer Onderzoek (08504, 12509)
- NANONET COST (BM1002)
- Netherlands Organization for Scientific Research (865.09.003)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- Alzheimer's disease, reactive astrocytes, microglia, APP/PS1 mice, neuroinflammation, gene expression profiling, neural communication, phagocytosis, endocytosis, amyloid plaques, cognitive decline
- MeSH terms
- Alzheimer Disease, Animals, Astrocytes, Cell Separation, Cells, Cultured, Cerebral Cortex, Cognition, Disease Models, Animal, Endocytosis, Humans, Inflammation, Mice, Transgenic, Synaptic Transmission, Phagocytosis, Gene Expression, Microglia
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