Dataset Information

Increased CSF Soluble TREM2 Concentration in Patients With Neurosyphilis.

ABSTRACT: Objective: To explore cerebrospinal fluid (CSF) levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and neurofilament light proteins (NFL) in patients with neurosyphilis (NS). Methods: We enrolled 71 NS patients (41 early-NS and 30 late-NS patients) and 20 syphilis but non-NS patients whose CSF samples were collected. The CSF levels of the microglial activation biomarker sTREM2 and neuronal injury biomarker NFL were measured using ELISA. Results: CSF sTREM2 levels were significantly higher in NS patients compared to those in syphilis/non-NS patients (p < 0.001). In a subgroup analysis, the CSF sTREM2 levels elevated significantly in late-NS patients than those in early-NS patients (p < 0.001). The CSF sTREM2 levels in early-NS group were also significantly higher than those in syphilis/non-NS group (p = 0.024). Like CSF sTREM2, similar differences between groups were also found in CSF NFL. There was a moderate correlation between CSF sTREM2 and CSF NFL (r = 0.406, p < 0.001) in NS group. Conclusions: CSF sTREM2 levels elevated in NS and peaked at the late stage, suggesting that CSF sTREM2 may be a useful marker to quantify microglia activation in NS and may play a role in the progression of NS. The positive correlation between CSF sTREM2 and CSF NFL indicates a linkage between microglial activation and neuronal injury in NS.

SUBMITTER: Li W

PROVIDER: S-EPMC7013092 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Increased CSF Soluble TREM2 Concentration in Patients With Neurosyphilis.

Li Wurong W Chang Haoxiao H Wu Wenqing W Xu Dongmei D Jiang Meijuan M Gao Junhua J Huang Yuming Y Xu Yun Y Yin Linlin L Zhang Xinghu X

Frontiers in neurology 20200205

Objective: To explore cerebrospinal fluid (CSF) levels of soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and neurofilament light proteins (NFL) in patients with neurosyphilis (NS). Methods: We enrolled 71 NS patients (41 early-NS and 30 late-NS patients) and 20 syphilis but non-NS patients whose CSF samples were collected. The CSF levels of the microglial activation biomarker sTREM2 and neuronal injury biomarker NFL were measured using ELISA. Results: CSF ...[more]

PMID: 32117023

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Project description:BackgroundTREM2 is a transmembrane receptor expressed by myeloid cells and acts to regulate their immune response. TREM2 governs the response of microglia to amyloid and tau pathologies in the Alzheimer's disease (AD) brain. TREM2 is also present in a soluble form (sTREM2), and its CSF levels fluctuate as a function of AD progression. Analysis of stroke and AD mouse models revealed that sTREM2 proteins bind to neurons, which suggests sTREM2 may act in a non-cell autonomous manner to influence neuronal function. sTREM2 arises from the proteolytic cleavage of the membrane-associated receptor. However, alternatively spliced TREM2 species lacking a transmembrane domain have been postulated to contribute to the pool of sTREM2. Thus, both the source of sTREM2 species and its actions in the brain remain unclear.MethodsThe expression of TREM2 isoforms in the AD brain was assessed through the analysis of the Accelerating Medicines Partnership for Alzheimer's Disease Consortium transcriptomics data, as well as qPCR analysis using post-mortem samples of AD patients and of the AD mouse model 5xFAD. TREM2 cleavage and secretion were studied in vitro using HEK-293T and HMC3 cell lines. Synaptic plasticity, as evaluated by induction of LTP in hippocampal brain slices, was employed as a measure of sTREM2 actions.ResultsThree distinct TREM2 transcripts, namely ENST00000373113 (TREM2230), which encodes the full-length transmembrane receptor, and the alternatively spliced isoforms ENST00000373122 (TREM2222) and ENST00000338469 (TREM2219), are moderately increased in specific brain regions of patients with AD. We provide experimental evidence that TREM2 alternatively spliced isoforms are translated and secreted as sTREM2. Furthermore, our functional analysis reveals that all sTREM2 species inhibit LTP induction, and this effect is abolished by the GABAA receptor antagonist picrotoxin.ConclusionsTREM2 transcripts can give rise to a heterogeneous pool of sTREM2 which acts to inhibit LTP. These results provide novel insight into the generation, regulation, and function of sTREM2 which fits into the complex biology of TREM2 and its role in human health and disease. Given that sTREM2 levels are linked to AD pathogenesis and progression, our finding that sTREM2 species interfere with LTP furthers our understanding about the role of TREM2 in AD.

Dataset Information

Increased CSF Soluble TREM2 Concentration in Patients With Neurosyphilis.

Publications

Increased CSF Soluble TREM2 Concentration in Patients With Neurosyphilis.

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