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Individuals with Down syndrome (DS) develop Alzheimer's disease (AD)-related neuropathology, characterized by amyloid plaques with amyloid β (Aβ) and neurofibrillary tangles with tau accumulation. Peripheral inflammation and the innate immune response are elevated in DS. Triggering receptor expressed in myeloid cells 2 ( TREM2 ) genetic variants are risk factors for AD and other neurodegenerative diseases. Soluble TREM2 (sTREM2), a soluble cleavage product of TREM2, is elevated in AD cerebrospinal fluid and positively correlates with cognitive decline. There is relatively little information about TREM2 in DS. Our objective was to examine the relationship between sTREM2 and inflammatory markers in young adults with DS, prior to the development of dementia symptoms. Because TREM2 plays a role in the innate immune response and has been associated with dementia, the hypothesis of this exploratory study was that young adults with DS predementia ( n = 15, mean age = 29.5 y) would exhibit a different relationship between sTREM2 and inflammatory markers in plasma, compared with neurotypical, age-matched controls ( n = 16, mean age = 29.6 y). Indeed, young adults with DS had significantly elevated plasma sTREM2 and inflammatory markers. Additionally, in young adults with DS, sTREM2 correlated positively with 24 of the measured cytokines, whereas there were no significant correlations in the control group. Hierarchical clustering of sTREM2 and cytokine concentrations also differed between the groups, supporting the hypothesis that its function is altered in people with DS predementia. This preliminary report of human plasma provides a basis for future studies investigating the relationship between TREM2 and the broader immune response predementia.

An Altered Relationship between Soluble TREM2 and Inflammatory Markers in Young Adults with Down Syndrome: A Preliminary Report