Increased cerebrospinal fluid soluble TREM2 concentration in Alzheimer’s disease

Molecular Neurodegeneration

Henrik Zetterberg⁴  Kevin Mills³  Jonathan Schott²  John Hardy⁶  Kaj Blennow⁴  Annika Öhrfelt⁴  Per Johansson¹  Johan Svensson⁵  Nadia Magdalinou²  Ross Paterson²  Wendy Heywood³  Amanda Heslegrave⁶ 

[1] Department of Endocrinology, Skaraborg Hospital, Skövde S-541 85, Sweden;Dementia Research Centre UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK;UCL Institute of Child Health, Guilford Street, London WC1N 1EH, UK;Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal S-431 80, Sweden;Department of Internal Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg S-413 45, Sweden;Department of Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK

关键词: TREM2;    Cerebrospinal fluid;    Microglia;    Alzheimer’s disease;   

Others  :  1235471
DOI  :  10.1186/s13024-016-0071-x

 received in 2015-09-30, accepted in 2016-01-06,  发布年份 2016

【 摘 要 】

Background

The discovery that heterozygous missense mutations in the gene encoding triggering receptor expressed on myeloid cells 2 (TREM2) are risk factors for Alzheimer’s disease (AD), with only the apolipoprotein E (APOE) ε4 gene allele conferring a higher risk, has led to increased interest in immune biology in the brain. TREM2 is expressed on microglia, the resident immune cells of the brain and has been linked to phagocytotic clearance of amyloid β (Aβ) plaques. Soluble TREM2 (sTREM2) has previously been measured in cerebrospinal fluid (CSF) by ELISA but in our hands commercial kits have proved unreliable, suggesting that other methods may be required. We developed a mass spectrometry method using selected reaction monitoring for the presence of a TREM2 peptide, which can be used to quantify levels of sTREM2 in CSF.

Findings

We examined CSF samples from memory clinics in Sweden and the UK. For all samples the following were available: clinical diagnosis, age, sex, and measurements of the CSF AD biomarkers Aβ42, T-tau and P-tau ₁₈₁ . AD patients (n = 37) all met biomarker (IWG2) criteria for AD. Control individuals (n = 22) were cognitively normal without evidence for AD in CSF. We found significantly higher sTREM2 concentration in AD compared to control CSF. There were significant correlations between CSF sTREM2 and T-tau as well as P-tau ₁₈₁ . CSF sTREM2 increase in AD was replicated in a second, independent cohort consisting of 24 AD patients and 16 healthy volunteers.

Conclusion

CSF concentrations of sTREM2 are higher in AD than in controls, and correlate with markers of neurodegeneration. CSF sTREM2 may be used to quantify glial activation in AD.

【 授权许可】

   
2016 Heslegrave et al.

【 图 表 】

Fig. 1.

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