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

Alzheimer's & Dementia - Tập 12 - Trang 1132-1148 - 2016
M. Florencia Iulita1, Alison Ower2, Concetta Barone3, Rowan Pentz4, Palma Gubert1, Corrado Romano3, Rita Anna Cantarella5, Flaviana Elia3, Serafino Buono3, Marilena Recupero3, Carmelo Romano3, Sabrina Castellano6, Paolo Bosco3, Santo Di Nuovo6, Filippo Drago7, Filippo Caraci3,8, A. Claudio Cuello1,4,9
1Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada
2Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom
3IRCCS Associazione Oasi Maria SS, Institute for Research On Mental Retardation and Brain Aging, Troina, Italy
4Department of Neurology and Neurosurgery, McGill University, Montreal, Canada
5ANFFAS-Catania, Catania, Italy
6Department of Educational Sciences, University of Catania, Catania, Italy
7Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy
8Department of Drug Sciences, University of Catania, Catania, Italy
9Department of Anatomy and Cell Biology, McGill University, Montreal, Canada

Tóm tắt

AbstractIntroductionGiven that Alzheimer's pathology develops silently over decades in Down syndrome (DS), prognostic biomarkers of dementia are a major need.MethodsWe 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.ResultsAβ40 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.ConclusionsOur findings support the combination of plasma and cognitive assessments for the identification of DS individuals at risk of dementia.

Tài liệu tham khảo

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Alzheimer's & Dementia

Tập 12

1132-1148

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