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.

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

C. Romano;S. Castellano;DI NUOVO, Santo;DRAGO, Filippo;CARACI, FILIPPO;
2016-01-01

Abstract

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.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/44447
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