An inflammatory and trophic disconnect biomarker profile revealed in Down syndrome plasma: relation to cognitive decline and longitudinal evaluation

Introduction: Given that Alzheimer’s pathology develops silently over decades in Down syndrome(DS), prognostic biomarkers of dementia are a major need.Methods: We investigated the plasma levels of Ab, proNGF, tPA, neuroserpin, metallo-proteasesand inflammatory molecules in 31 individuals with DS (with and without dementia) and in 31 healthycontrols. We examined associations between biomarkers and cognitive decline.Results: Ab40 and Ab42 were elevated in DS plasma compared to controls, even in DS individualswithout dementia. Plasma Ab correlated with the rate of cognitive decline across 2 years. ProNGF,MMP-1, MMP-3, MMP-9 activity, TNF-a, IL-6, and IL-10 were higher in DS plasma, even atAD-asymptomatic stages. Declining plasma Ab42 and increasing proNGF levels correlated withcognitive decline. A combined measure of Ab and inflammatory molecules was a strong predictorof prospective cognitive deterioration.Conclusions: Our findings support the combination of plasma and cognitive assessments for theidentification of DS individuals at risk of dementia.