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

作者：Iulita M Florencia; Ower Alison; Barone Concetta; Pentz Rowan; Gubert Palma; Romano Corrado; Cantarella Rita Anna; Elia Flaviana; Buono Serafino; Recupero Marilena; Romano Carmelo; Castellano Sabrina; Bosco Paolo; Santo Di Nuovo; Drago Filippo; Caraci Filippo; Cuello A Claudio

来源：ALZHEIMERS %26 DEMENTIA, 2016, 12(11): 1132-1148.

DOI：10.1016/j.jalz.2016.05.001

• Alzheimer's disease
• Amyloid-beta
• Biomarker
• Blood
• Down syndrome
• Inflammation
• Nerve growth factor
• Metallo-proteases
• MMP-3
• MMP-9
• Plasma
• proNGF

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 A beta, 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: A beta 40 and A beta 42 were elevated in DS plasma compared to controls, even in DS individuals without dementia. Plasma A beta correlated with the rate of cognitive decline across 2 years. ProNGF, MMP-1, MMP-3, MMP-9 activity, TNF-alpha, IL-6, and IL-10 were higher in DS plasma, even at AD-asymptomatic stages. Declining plasma A beta 42 and increasing proNGF levels correlated with cognitive decline. A combined measure of A beta 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.

• 出版日期2016-11