Abstract
Background/aims
Recently, we showed that triggering receptor expressed on myeloid cells 1 (TREM1) was involved in the pathogenesis of Alzheimer’s disease (AD) since it modulated microglial phagocytic functions and thus affected amyloid-β clearance in the brain. Interestingly, a soluble form of TREM1 (sTREM1) can be detected in the plasma of human. To date, whether sTREM1 concentrations were altered in the plasma under AD context remained unclear.
Methods
In this study, we compared the plasma concentrations of sTREM1 between 110 AD patients and 128 age- and gender-matched controls. Meanwhile, the relationship of sTREM1 concentrations with total tau levels in the plasma of AD patients was also assessed.
Results
We revealed that the concentrations of sTREM1 were significantly increased in AD patients. Meanwhile, the sTREM1 concentrations were gradually increased during disease progression. More importantly, we showed that the sTREM1 concentrations were positively correlated with the levels of total tau in the plasma of AD patients (r = 0.61, P < 0.001). The subsequent subgroup analysis indicated that this correlation was more pronounced in patients with severe dementia (Mini-Mental State Exam score < 10, r = 0.81, P < 0.01).
Conclusion
These findings indicate a potential association between sTREM1 and tau pathology, and further confirm an involvement of this immune receptor in AD pathogenesis.
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References
Jiang T, Yu JT, Tian Y et al (2013) Epidemiology and etiology of Alzheimer’s disease: from genetic to non-genetic factors. Curr Alzheimer Res 10:852–867
Scheltens P, Blennow K, Breteler MM et al (2016) Alzheimer’s disease. Lancet 388:505–517. https://doi.org/10.1016/S0140-6736(15)01124-1
Jiang T, Yu JT, Tan L (2012) Novel disease-modifying therapies for Alzheimer’s disease. J Alzheimer’s Dis JAD 31:475–492. https://doi.org/10.3233/JAD-2012-120640
Replogle JM, Chan G, White CC et al (2015) A TREM1 variant alters the accumulation of Alzheimer-related amyloid pathology. Ann Neurol 77:469–477. https://doi.org/10.1002/ana.24337
Saadipour K (2017) TREM1: a potential therapeutic target for Alzheimer’s disease. Neurotox Res 32:14–16. https://doi.org/10.1007/s12640-017-9716-y
Sao T, Yoshino Y, Yamazaki K et al (2018) TREM1 mRNA expression in leukocytes and cognitive function in Japanese patients with alzheimer’s disease. J Alzheimer’s Dis JAD 64:1275–1284. https://doi.org/10.3233/JAD-180418
Jiang T, Zhang YD, Gao Q et al (2016) TREM1 facilitates microglial phagocytosis of amyloid beta. Acta Neuropathol 132:667–683. https://doi.org/10.1007/s00401-016-1622-5
Jeremie L, Amir B, Marc D et al (2015) The triggering receptor expressed on myeloid cells-1: a new player during acute myocardial infarction. Pharmacol Res 100:261–265. https://doi.org/10.1016/j.phrs.2015.07.027
Charles PE, Noel R, Massin F et al (2016) Significance of soluble triggering receptor expressed on myeloid cells-1 elevation in patients admitted to the intensive care unit with sepsis. BMC Infect Dis 16:559. https://doi.org/10.1186/s12879-016-1893-4
Boufenzer A, Lemarie J, Simon T et al (2015) TREM-1 mediates inflammatory injury and cardiac remodeling following myocardial infarction. Circ Res 116:1772–1782. https://doi.org/10.1161/CIRCRESAHA.116.305628
Sun XG, Ma Q, Jing G et al (2017) Early elevated levels of soluble triggering receptor expressed on myeloid cells-1 in subarachnoid hemorrhage patients. Neurol Sci 38:873–877. https://doi.org/10.1007/s10072-017-2853-5
Jiang T, Tan L, Gao Q et al (2016) Plasma angiotensin-(1–7) is a potential biomarker for Alzheimer’s disease. Curr Neurovascular Res 13:96–99
McKhann G, Drachman D, Folstein M et al (1984) Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 34:939–944
Klesney-Tait J, Turnbull IR, Colonna M (2006) The TREM receptor family and signal integration. Nature Immunol 7:1266–1273. https://doi.org/10.1038/ni1411
Gibot S, Kolopp-Sarda MN, Bene MC et al (2004) A soluble form of the triggering receptor expressed on myeloid cells-1 modulates the inflammatory response in murine sepsis. J Exp Med 200:1419–1426. https://doi.org/10.1084/jem.20040708
Begum NA, Ishii K, Kurita-Taniguchi M et al (2004) Mycobacterium bovis BCG cell wall-specific differentially expressed genes identified by differential display and cDNA subtraction in human macrophages. Infect Immun 72:937–948
Gomez-Pina V, Soares-Schanoski A, Rodriguez-Rojas A et al (2007) Metalloproteinases shed TREM-1 ectodomain from lipopolysaccharide-stimulated human monocytes. J Immunol 179:4065–4073
Guo T, Noble W, Hanger DP (2017) Roles of tau protein in health and disease. Acta Neuropathol 133:665–704. https://doi.org/10.1007/s00401-017-1707-9
Orr ME, Sullivan AC, Frost B (2017) A brief overview of tauopathy: causes, consequences, and therapeutic strategies. Trends Pharmacol Sci 38:637–648. https://doi.org/10.1016/j.tips.2017.03.011
Montagne A, Zhao Z, Zlokovic BV (2017) Alzheimer’s disease: a matter of blood-brain barrier dysfunction? J Exp Med 214:3151–3169. https://doi.org/10.1084/jem.20171406
Mattsson N, Zetterberg H, Janelidze S et al (2016) Plasma tau in Alzheimer disease. Neurology 87:1827–1835. https://doi.org/10.1212/WNL.0000000000003246
Olsson B, Lautner R, Andreasson U et al (2016) CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol 15:673–684. https://doi.org/10.1016/S1474-4422(16)00070-3
Mielke MM, Hagen CE, Wennberg AMV et al (2017) Association of plasma total tau level with cognitive decline and risk of mild cognitive impairment or dementia in the mayo clinic study on aging. JAMA Neurol 74:1073–1080. https://doi.org/10.1001/jamaneurol.2017.1359
Acknowledgements
This work was supported by National Natural Science Foundation of China (81501092), Natural Science Foundation of Jiangsu Province (BK20150091), “Six Talent Summit” Foundation of Jiangsu Province (2016-WSN-180), Youth Medical Talent Program of Jiangsu Province (QNRC2016068), Medical Innovation Team of Jiangsu Province (CXTDA2017030), and Nanjing Medical Science and Technology Development Foundation for Distinguished Young Scholars (JQX17008).
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Jiang, T., Gong, PY., Tan, MS. et al. Soluble TREM1 concentrations are increased and positively correlated with total tau levels in the plasma of patients with Alzheimer’s disease. Aging Clin Exp Res 31, 1801–1805 (2019). https://doi.org/10.1007/s40520-019-01122-9
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DOI: https://doi.org/10.1007/s40520-019-01122-9