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

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

Research output: Contribution to journalArticle

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 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.

Original languageEnglish
Pages (from-to)1132-1148
Number of pages17
JournalAlzheimer's and Dementia
Volume12
Issue number11
DOIs
Publication statusPublished - Nov 1 2016

Keywords

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

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Geriatrics and Gerontology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

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    Iulita, M. F., Ower, A., Barone, C., Pentz, R., Gubert, P., Romano, C., Cantarella, R. A., Elia, F., Buono, S., Recupero, M., Castellano, S., Bosco, P., Di Nuovo, S., Drago, F., Caraci, F., & Cuello, A. C. (2016). An inflammatory and trophic disconnect biomarker profile revealed in Down syndrome plasma: Relation to cognitive decline and longitudinal evaluation. Alzheimer's and Dementia, 12(11), 1132-1148. https://doi.org/10.1016/j.jalz.2016.05.001