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Updated: Jul 4, 2026
Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques
Published on: June 1, 2016
TREM2 is upregulated in amyloid plaque-associated microglia in aged APP23 transgenic mice
Stefanie Frank1, Guido J Burbach, Michael Bonin
1Institute of Clinical Neuroanatomy, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, Frankfurt am Main, Germany.
Abstract:
Alzheimer's disease (AD) is characterized by extracellular deposits of amyloid-beta protein which attract dense clusters of microglial cells. Here, we analyzed amyloid plaque-associated areas in aged APP23 transgenic mice, an animal model of AD, by combining laser microdissection with microarray analysis and quantitative RT-PCR (qPCR). By comparing gene expression profiles, we found that 538 genes (1.3% of a total of 41,234 analyzed genes) were differentially expressed in plaque-associated versus plaque-free tissue of aged APP23 transgenic mice. One of these genes is the microglia-associated triggering receptor expressed on myeloid cells (TREM2) which enhances phagocytosis, but abrogates cytokine production as well as TLR and Fc receptor-mediated induction of TNF secretion. Western Blot analysis demonstrated an upregulation of TREM2 protein in APP23 transgenic compared with nontransgenic mice. Confocal imaging studies, furthermore, confirmed colocalization of TREM2 protein with microglia. Thus, when TREM2 is induced on microglia in plaque-loaded brain areas the respective signaling may prevent inflammation-induced bystander damage of neurons. At the same time, TREM2 signaling may also account for the failure to sufficiently eliminate extracellular amyloid with the help of a systemic immune response.
Insights
Alzheimer's disease involves amyloid plaques and microglial cells. The study found TREM2 gene expression increases near plaques, potentially reducing inflammation but hindering amyloid clearance.
Area of Science:
- Neuroscience
- Immunology
- Genetics
Background:
- Alzheimer's disease (AD) is marked by amyloid-beta plaques and microglial cell aggregation.
- Microglia play a crucial role in AD pathogenesis and brain inflammation.
Purpose of the Study:
- To investigate gene expression changes in microglial cells associated with amyloid plaques in an AD mouse model.
- To identify specific genes, like TREM2, involved in the microglial response to amyloid pathology.
Main Methods:
- Laser microdissection combined with microarray analysis and qPCR in aged APP23 transgenic mice.
- Western Blot and confocal imaging to validate TREM2 protein expression and localization.
Main Results:
- 538 genes were differentially expressed in plaque-associated versus plaque-free brain tissue.
- TREM2 (triggering receptor expressed on myeloid cells 2) was significantly upregulated in plaque-associated microglia.
- TREM2 protein colocalized with microglia in amyloid plaque areas.
Conclusions:
- TREM2 induction in microglia near amyloid plaques may protect neurons from inflammation-induced damage.
- TREM2 signaling might also impair the efficient clearance of extracellular amyloid by the immune system.
