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Updated: Nov 8, 2025
Detection of Abnormal Prion Protein by Immunohistochemistry
Published on: May 5, 2023
TREM2 expression in the brain and biological fluids in prion diseases
Daniela Diaz-Lucena1,2, Niels Kruse3, Katrin Thüne4
1Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), L'Hospitalet de Llobregat, Spain.
Abstract:
Triggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated. In the present study, we analysed the expression of TREM2 and its main sheddase ADAM10 in the brain of sporadic Creutzfeldt-Jakob disease (sCJD) patients and evaluated the role of CSF and plasma sTREM2 as a potential diagnostic marker of prion disease. Our data indicate that, compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia. In contrast, ADAM10 is increased at the protein, but not the mRNA level, with a restricted neuronal expression. Elevated CSF sTREM2 is found in sCJD, genetic CJD with mutations E200K and V210I in the prion protein gene (PRNP), and iatrogenic CJD, as compared to healthy controls (HC) (AUC = 0.78-0.90) and neurological controls (AUC = 0.73-0.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer's disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are PRNP codon 129 and subtype-related, correlate with CSF 14-3-3 positivity, total-tau and YKL-40, and increase with disease progression. In plasma, sTREM2 is increased in sCJD compared with HC (AUC = 0.80), displaying positive correlations with plasma total-tau, neurofilament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fluids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratification, and disease monitoring.
Insights
Triggering receptor expressed on myeloid cells 2 (TREM2) is elevated in prion diseases, with soluble TREM2 (sTREM2) in cerebrospinal fluid and plasma showing diagnostic potential. TREM2 alterations in the brain correlate with disease subtypes and progression.
Area of Science:
- Neuroscience
- Immunology
- Biochemistry
Background:
- Triggering receptor expressed on myeloid cells 2 (TREM2) is a key regulator of microglial function in neurodegenerative diseases.
- The role of TREM2 in prion diseases, a group of rapidly progressive dementias, requires further elucidation.
- Soluble TREM2 (sTREM2) is generated by shedding of the TREM2 ectodomain.
Purpose of the Study:
- To analyze TREM2 and its sheddase ADAM10 expression in sporadic Creutzfeldt-Jakob disease (sCJD) brains.
- To evaluate cerebrospinal fluid (CSF) and plasma sTREM2 as potential diagnostic markers for prion diseases.
- To investigate the relationship between sTREM2 levels and disease characteristics in sCJD.
Main Methods:
- Analysis of TREM2 and ADAM10 mRNA and protein expression in sCJD patient brains.
- Quantification of sTREM2 levels in CSF and plasma from patients with various prion diseases, Alzheimer's disease, multiple sclerosis, and healthy controls.
- Correlation analysis of sTREM2 levels with clinical and biomarker data in sCJD.
Main Results:
- TREM2 mRNA and protein levels are increased in sCJD brains in a region- and subtype-dependent manner.
- ADAM10 protein, but not mRNA, is increased in sCJD brains with restricted neuronal expression.
- Elevated CSF sTREM2 is observed in sCJD, genetic CJD (E200K, V210I), and iatrogenic CJD, showing high diagnostic accuracy (AUC 0.73-0.90).
- CSF sTREM2 is unchanged in fatal familial insomnia, Alzheimer's disease, and multiple sclerosis.
- CSF sTREM2 in sCJD correlates with PRNP codon 129 genotype, subtype, CSF 14-3-3, total-tau, YKL-40, and disease progression.
- Plasma sTREM2 is increased in sCJD (AUC 0.80) and correlates with plasma total-tau, neurofilament light, and YKL-40.
Conclusions:
- TREM2 is altered in human prion diseases, with altered expression in brain tissue.
- CSF and plasma sTREM2 demonstrate significant potential as diagnostic biomarkers for prion diseases.
- sTREM2 may serve as a valuable tool for target engagement, patient stratification, and disease monitoring in prion diseases.
