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 Aβ, proNGF, tPA, neuroserpin, metallo-proteases and inflammatory molecules in 31 individuals with DS (with and without dementia) and in 31 healthy controls. We examined associations between biomarkers and cognitive decline.
Results: Aβ40 and Aβ42 were elevated in DS plasma compared to controls, even in DS individuals without dementia. Plasma Aβ correlated with the rate of cognitive decline across 2 years. ProNGF, MMP-1, MMP-3, MMP-9 activity, TNF-α, IL-6, and IL-10 were higher in DS plasma, even at AD-asymptomatic stages. Declining plasma Aβ42 and increasing proNGF levels correlated with cognitive decline. A combined measure of Aβ and inflammatory molecules was a strong predictor of prospective cognitive deterioration.
Conclusions: Our findings support the combination of plasma and cognitive assessments for the identification of DS individuals at risk of dementia.
Keywords: Alzheimer's disease; Amyloid-β; Biomarker; Blood; Down syndrome; Inflammation; MMP-3; MMP-9; Metallo-proteases; Nerve growth factor; Plasma; proNGF.
Copyright © 2016 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.