Increase in the density of resting microglia precedes neuritic plaque formation and microglial activation in a transgenic model of Alzheimer's disease
Open accessAbstract
The formation of cerebral senile plaques composed of amyloid β peptide (Aβ) is a fundamental feature of Alzheimer's disease (AD). Glial cells and more specifically microglia become reactive in the presence of Aβ. In a triple transgenic model of AD (3 × Tg-AD), we found a significant increase in activated microglia at 12 (by 111%) and 18 (by 88%) months of age when compared with non-transgenic (non-Tg) controls. This microglial activation correlated with Aβ plaque formation, and the activation in microglia was closely associated with Aβ plaques and smaller Aβ deposits. We also found a significant increase in the area density of resting microglia in 3 × Tg-AD animals both at plaque-free stage (at 9 months by 105%) and after the development of A plaques (at 12 months by 54% and at 18 months by 131%). Our results show for the first time that the increase in the density of resting microglia precedes both plaque formation and activation of microglia by extracellular Aβ accumulation. We suggest that AD pathology triggers a complex microglial reaction: at the initial stages of the disease the number of resting microglia increases, as if in preparation for the ensuing activation in an attempt to fight the extracellular Aβ load that is characteristic of the terminal stages of the disease.
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Classically, denser microglial populations might indicate a higher level of surveillance of the brain parenchyma, although this feature has also been reported to precede a reactive state.
“Classically, denser microglial populations might indicate a higher level of surveillance of the brain parenchyma, although this feature has also been reported to precede a reactive state [79].”
From Sex chromosomes and sex hormones differently shape microglial properties during normal physiological conditions in the adult mouse hippocampus (2025) · cites this paper as [79]
The Discussion (page unavailable) reports that increased resting-microglial density in an Alzheimer’s mouse model preceded plaque formation and microglial activation. The introductory passage (page unavailable) says resting microglia scan their surroundings, but the paper does not establish that denser populations provide a higher level of surveillance. (LLM, conf=0.84)
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“Classically, denser microglial populations might indicate a higher level of surveillance of the brain parenchyma, although this feature has also been reported to precede a reactive state [79].”
- Authors
- Rodríguez, J. J., Witton, J., Olabarria, M., Noristani, H. N., & Verkhratsky, A.
- Affiliations
- University of Manchester (GB)
- Venue
- Cell Death & Disease
- Published
- 2010-01-14
- Volume
- 1
- Issue
- 1
- Pages
- e1-e1
- ISSN
- 2041-4889 (ISSN-L)
- PMC
- PMC3032511
- OpenAlex
- W2071227315
- Cited by
- 114
- References
- 11
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 5 · 2023: 8 · 2022: 11 · 2021: 7 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 4 · 2015: 4 · 2014: 8 · 2013: 9 · 2012: 9
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- www.springer.com/tdm (unspecified)
- Locations
- Cell Death and Disease (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- Communities in ADDI (University of the Basque Country) (submittedVersion, other-oa)
- ASEP (submittedVersion, public-domain)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by)
- Hispana (submittedVersion, other-oa)
- Funders
- Alzheimer's Research Trust (ART/PG2004A/1)
- Grantová Agentura České Republiky (GA309/09/1696, GA305/08/1384)
- 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
- Alzheimer's disease, microglia, microglial activation, amyloid-beta, amyloid plaques, triple transgenic mouse model, neuroinflammation
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Mice, Transgenic, Time Factors, Amyloid beta-Peptides, Microglia, Mice, Plaque, Amyloid
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