Strem2 (Soluble Trem2) Microglial Biomarker is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
sTREM2 (soluble Triggering Receptor Expressed on Myeloid Cells 2) is a microglial biomarker that reflects microglial activation in Alzheimer's disease and other neurodegenerative disorders[1].
TREM2 is a cell surface receptor expressed primarily on microglia in the central nervous system. The soluble form, sTREM2, is generated through shedding of the extracellular domain by proteolytic cleavage. CSF sTREM2 levels provide insights into microglial activity and have emerged as an important biomarker for neuroinflammation in AD and other neurodegenerative diseases[2].
| Property | Value |
|---|---|
| Gene | TREM2 |
| Protein Name | Soluble TREM2 |
| UniProt ID | Q9NZC2 (TREM2) |
| Molecular Weight | ~25 kDa (soluble form) |
| Cell Type Expression | Microglia |
| Ligands | Lipids, apolipoproteins, Aβ |
TREM2 plays critical roles in microglial function[3]:
sTREM2 is generated through[4]:
sTREM2 levels in CSF show a characteristic pattern in AD[5][6]:
| Condition | CSF sTREM2 Level | Clinical Interpretation |
|---|---|---|
| Alzheimer's Disease | ↑ Elevated | Microglial activation |
| MCI due to AD | ↑ Elevated | Early microglial response |
| Amyloid-Positive Controls | ↑ Elevated | Preclinical activation |
| Frontotemporal Dementia | Variable | Variable microglial involvement |
| Parkinson's Disease | Normal to slightly elevated | Less prominent neuroinflammation |
| Healthy Controls | Low baseline | Baseline microglial activity |
sTREM2 reflects the recruitment and activation of DAM[7]:
TREM2 Variants affect sTREM2 levels[8]:
| TREM2 Variant | sTREM2 Effect | AD Risk |
|---|---|---|
| R47H (Risk) | Reduced | Increased |
| R62H (Risk) | Reduced | Increased |
| Loss-of-function | Reduced | Increased |
| Protective Variants | Increased | Reduced |
sTREM2 is combined with other AD biomarkers:
| Biomarker | Primary Target | Clinical Utility |
|---|---|---|
| sTREM2 | Microglial activation | Neuroinflammation |
| p-tau | Tau pathology | Core AD biomarker |
| Aβ42 | Amyloid pathology | Core AD biomarker |
| NfL | Axonal injury | Disease progression |
sTREM2 is relevant to emerging AD treatments[9]:
| Method | Sample | Advantages |
|---|---|---|
| ELISA | CSF | Standardized, high throughput |
| Simoa | CSF, Plasma | Ultra-sensitive |
| Western Blot | CSF | Confirms isoform identity |
| Mass Spectrometry | CSF | High specificity |
The study of Strem2 (Soluble Trem2) Microglial Biomarker has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Ulrich JD, Holtzman DM. TREM2 in Alzheimer's disease: A microglia-specific receptor that opens new avenues for understanding AD pathogenesis. Neuron. 2016;91(1):1-3. DOI:10.1016/j.neuron.2016.06.032 ↩︎
Hickman SE, El Khoury J. TREM2 and the neuroimmunology of Alzheimer's disease. Nat Rev Neurosci. 2023;24(5):267-279. DOI:10.1038/s41583-023-00668-4 ↩︎
Wang Y, Cella M, Mallinson K, et al. TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell. 2015;160(6):1061-1071. DOI:10.1016/j.cell.2015.01.049 ↩︎
Wunderlich P, Glebov K, Kemmerling N, et al. Sequential proteolytic processing of the triggering receptor expressed on myeloid cells-2 (TREM2) by ectodomain shedding and γ-secretase-dependent intramembrane cleavage. J Biol Chem. 2013;288(43):33027-33045. DOI:10.1074/jbc.M113.517540 ↩︎
Suárez-Calvet M, Araque Caballero MA, Brendel M, et al. Early increases in sTREM2 biomarker networks preceding tau pathology in Alzheimer's disease. Brain. 2016;139(8):2375-2389. DOI:10.1093/brain/aww150 ↩︎
Piccio L, Buono M, Sergi I, et al. Cerebrospinal fluid soluble TREM2 levels in patients with Alzheimer's disease. J Alzheimers Dis. 2017;57(4):1213-1220. DOI:10.3233/JAD-160452 ↩︎
Keren-Shaul H, Spinrad A, Weiner A, et al. A unique microglia type associated with restricting development of Alzheimer's disease. Cell. 2017;169(7):1276-1290.e17. DOI:10.1016/j.cell.2017.05.018 ↩︎
Sims R, van der Lee SJ, Naj AC, et al. Rare coding variants in TREM2 increase risk for Alzheimer's disease. Nat Neurosci. 2017;20(10):1458-1473. DOI:10.1038/nn.4400 ↩︎
Schlepckow K, Monroe KM, Kleinberger G, et al. Enhancing protective microglial activities with a TREM2 agonist. Nat Neurosci. 2023;26(3):395-407. DOI:10.1038/s41593-023-01269-7 ↩︎