Background:
Cerebrospinal fluid (CSF) biomarkers play a crucial role in the diagnosis of Alzheimer'sDisease (AD). Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane receptor expressed by microglia. Cleavage of TREM2 results in the formation of soluble TREM2 (sTREM2), which can be detected in the CSF. This study aimed to elucidate the relation between CSF sTREM2 levels and AD pathology in clinically and AT(N) classified groups.
Methods:
In this study, CSF samples of 262 Alzheimer's disease (AD) patients, 70 mild cognitive impairment (MCI) patients, and 37 cognitively unimpaired (CU) individuals were investigated. Cases were diagnosed according to the NIA-AA 2011 criteria, and CSF core biomarkers (Amyloid β (1-42), Phospho-Tau (181P), Total-Tau) indicating AT(N) classification, and sTREM2 levels were determined by ELISA. Statistical analysis was performed using SPSS Version 31.0.
Results:
Analysis revealed a statistically significant difference (p<0.001) in CSF sTREM2 levels among the AD, MCI, and CU groups. The highest CSF sTREM2 levels were observed in the AD group, compared to the MCI (p=0.019) and CU (p<0.001) groups. Furthermore, CSF sTREM2 levels were significantly higher (p<0.001) in the A+, T+, and (N+) groups, compared to their negative counterparts, namely A-, T-, and N- groups. The largest effect size was observed in the T+ vs T- comparison (Hedges’ g:0.89). In the MCI group, sTREM2 levels showed positive correlation with CSF Aβ (p=0.004), P-tau181 (p<0.001), and T-tau (p<0.001) levels. Within the AD group, the correlation between sTREM2 and Aβ was not statistically significant (p=0.063). However, T-tau and p-tau181 exhibited significant positive correlations (p<0.001).
Conclusion:
Our findings support previous studies and demonstrate that CSF sTREM2 levels are significantly increased in AD pathology. Furthermore, the correlation between sTREM and pTau(181) is not only in AD but also in non-AD MCI groups, but not in CU, which might indicate an early event for AD-type pathology in MCI. This might increase the potential of STREM2 to serve as a biomarker. It also supports the relationship between AD, microglial activation, and neurofibrillary tangle formation. This research was supported by TUBITAK (Project ID: 22AG017).