Advertisement

Soluble TREM1 concentrations are increased and positively correlated with total tau levels in the plasma of patients with Alzheimer’s disease

  • Teng JiangEmail author
  • Peng-Yu Gong
  • Meng-Shan Tan
  • Xiao Xue
  • Shi Huang
  • Jun-Shan Zhou
  • Lan Tan
  • Ying-Dong ZhangEmail author
Original Article

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.

Keywords

Alzheimer’s disease sTREM1 Tau Plasma Biomarker 

Notes

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).

Compliance with ethical standards

Conflict of interest

The authors confirm that this article has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of Qingdao Municipal Hospital and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

A written informed consent was obtained from each participant or the legal guardian.

References

  1. 1.
    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 10:852–867CrossRefGoogle Scholar
  2. 2.
    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 CrossRefGoogle Scholar
  3. 3.
    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 CrossRefGoogle Scholar
  4. 4.
    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 CrossRefGoogle Scholar
  5. 5.
    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 CrossRefGoogle Scholar
  6. 6.
    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 CrossRefGoogle Scholar
  7. 7.
    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 CrossRefGoogle Scholar
  8. 8.
    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 CrossRefGoogle Scholar
  9. 9.
    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 CrossRefGoogle Scholar
  10. 10.
    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 CrossRefGoogle Scholar
  11. 11.
    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 CrossRefGoogle Scholar
  12. 12.
    Jiang T, Tan L, Gao Q et al (2016) Plasma angiotensin-(1–7) is a potential biomarker for Alzheimer’s disease. Curr Neurovascular Res 13:96–99CrossRefGoogle Scholar
  13. 13.
    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 34:939–944CrossRefGoogle Scholar
  14. 14.
    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 CrossRefGoogle Scholar
  15. 15.
    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 CrossRefGoogle Scholar
  16. 16.
    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 72:937–948CrossRefGoogle Scholar
  17. 17.
    Gomez-Pina V, Soares-Schanoski A, Rodriguez-Rojas A et al (2007) Metalloproteinases shed TREM-1 ectodomain from lipopolysaccharide-stimulated human monocytes. J Immunol 179:4065–4073CrossRefGoogle Scholar
  18. 18.
    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 CrossRefGoogle Scholar
  19. 19.
    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 CrossRefGoogle Scholar
  20. 20.
    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 CrossRefGoogle Scholar
  21. 21.
    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 CrossRefGoogle Scholar
  22. 22.
    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 CrossRefGoogle Scholar
  23. 23.
    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 CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Teng Jiang
    • 1
    Email author
  • Peng-Yu Gong
    • 1
  • Meng-Shan Tan
    • 2
  • Xiao Xue
    • 1
  • Shi Huang
    • 1
  • Jun-Shan Zhou
    • 1
  • Lan Tan
    • 2
  • Ying-Dong Zhang
    • 1
    • 3
    Email author
  1. 1.Department of Neurology, Nanjing First HospitalNanjing Medical UniversityNanjingPeople’s Republic of China
  2. 2.Department of Neurology, School of Medicine, Qingdao Municipal HospitalQingdao UniversityQingdaoPeople’s Republic of China
  3. 3.School of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjingPeople’s Republic of China

Personalised recommendations