AbstractBackgroundTriggering receptor expressed on myeloid cells 2 (TREM2) is up‐regulated in activated microglia related neuroinflammation in Alzheimer’s disease (AD). Most magnetic resonance spectroscopy (MRS) studies consistently demonstrated neuroinflammatory changes with elevated glial marker myoinositol (MI) or MI/total creatine (tCr) and lower levels of neuronal marker N‐acetylasparate (NAA) or NAA/tCr in patients with AD. We propose that the higher systemic TREM2 expression measured by TREM2 mRNA expression in peripheral blood might be associated with the neuroinflammatory marker in MRS.MethodWe recruited subjects with mild cognitive impairment (MCI) and dementia due to AD from two teaching hospitals in Taiwan. All of the subjects underwent clinically functional assessments and a neuropsychological test battery. Quantitative estimates of TREM2 mRNA and the soluble form of TREM2 (an alternatively spliced TREM2 transcript (TREM2alt)) mRNA levels were measured. Proton magnetic resonance spectroscopy (MRS) was performed by using a 2 × 2 × 2 cm3 voxel situated in the midsagittal posterior cingulate cortex (PCC)/precuneus region. We analyzed the association between MRS and peripheral TREM2 mRNA expression.ResultIn total, 15 MCI patients and 26 AD patients were recruited. The mean age of MCI and AD patients was 72.1 ± 6.0 and 76.7 ± 7.6 years. The mean MMSE score was 25.8 ± 2.1 in MCI patients and 20.8 ± 3.4 in AD patients. The percentage of apolipoprotein (APOE) ɛ4 carrier status in MCI and AD patients was 21.4% and 38.5%. The correlation analysis showed the TREM2alt mRNA expression level was associated with MI/tCr at PCC in AD (r = ‐0.68, p < 0.001) and MCI (r = ‐0.63, p = 0.013) subjects, but TREM2 mRNA expression was not.ConclusionThe TREM2alt mRNA expression is associated with the MI/tCr at PCC in both AD and MCI patients, which suggested the peripheral soluble TREM2 expression might reflect the central neuroinflammatory changes in AD patients.