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TREM2 is an innate immune transmembrane protein expressed in microglia and involved in the regulation of inflammatory response and phagocytosis. A soluble fragment of the protein (sTREM2) can be quantified in the cerebrospinal fluid (CSF) and has been shown to be abnormally increased in the course of Alzheimer’s disease (AD). In this article we studied the neuroanatomical correlates of increased CSF sTREM2 along the clinicopathological continuum of AD.
One hundred and fourteen participants (45 control, 19 preclinical AD, 27 mild cognitive impairment [MCI] due to AD and 23 mild AD dementia) underwent CSF sTREM2 determinations and MRI scanning. We studied the association between CSF sTREM2 concentrations, gray matter volume, and water motion diffusivity and anisotropy across the different groups.
In MCI patients, a significant positive correlation between CSF sTREM2 values and gray matter volume was found in the bilateral inferior and middle temporal cortices, the precuneus, the supramarginal and angular gyri, after controlling by age, sex and pTau. On the other hand, a negative correlation with mean diffusivity was detected in overlapping regions, among others.
In early AD, augmented CSF sTREM2 levels correspond with cerebral MRI features typical of brain swelling, namely increased gray matter volume and restricted water diffusivity. These results support for a role of TREM2 in the regulation of the neuroinflammatory response to early neurodegeneration.