Evaluating the relationship between soluble triggering receptor expressed on myeloid cells 2 (sTREM2) and pathological substrates of Alzheimer’s disease (AD)

Abstract

AbstractBackgroundDeveloping novel biomarkers of Alzheimer’s disease (AD) is critical for early disease detection and intervention. sTREM2 has proposed to be an early marker of glial activation. However, there has been significant controversy about the function of sTREM2. This study investigated the relationship between cerebral spinal fluid (CSF) sTREM2, and pathological changes in AD.MethodWe included patients with mild cognitive impairment, AD and healthy controls (n= 493, mean age= 73.7, SD= 6.1) were recruited for the Alzheimer’s Disease Neuroimaging Initiative. All participants completed a T1‐weighted MPRAGE MRI, amyloid ([18F]AV45 or [18F]Florbetaben), [18F]AV1451 and [18F]FDG scans. Standard uptake ratio values were calculated in SPM12 to identify the glucose metabolic rate and tau deposition within cortical regions. Amyloid status (Aβ positive/Aβ negative) was determined from processed data using a whole brain cerebellar ratio with a cut‐off value of 1.11. Correlations between CSF measurements, ROI, and voxel‐wise analyses were conducted using data from ADNI.ResultROI analyses demonstrated that increased CSF sTREM2 was associated with increased amyloid load in the whole brain, temporal, parietal, and occipital lobes of MCI patients. Additionally, increased CSF sTREM2 was associated with decreased glucose metabolism in the Posterior cingulate and parietal lobe in MCI patients. On the other hand, CSF sTREM2 was not significantly correlated with pathological changes in AD patients. However, voxel‐wise analysis comparing Aβ+ MCI patients to Aβ‐ CN subjects showed that increased CSF sTREM2 levels were associated with greater Aβ deposition in temporal and motor regions, increased grey matter volume in frontal and parietal regions, and decreased grey matter volume in the MT gyrus.ConclusionsTREM2 levels are associated with amyloid deposition in MCI patients but not in the late stage of AD patients, this suggest that glial activation is associated early on the disease.