title: An inflammatory and trophic disconnect biomarker profile revealed in Down syndrome plasma: Relation to cognitive decline and longitudinal evaluation.
abstract: Given that Alzheimer's pathology develops silently over decades in Down syndrome (DS), prognostic biomarkers of dementia are a major need.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Our findings support the combination of plasma and cognitive assessments for the identification of DS individuals at risk of dementia.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
authors.forename: M Florencia
authors.initials: MF
authors.lastname: Iulita
authors.affiliation: Department of Infectious Disease Epidemiology, Imperial College London, United Kingdom.
authors.forename: Alison
authors.initials: A
authors.lastname: Ower
authors.affiliation: IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Barone
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
authors.forename: Rowan
authors.initials: R
authors.lastname: Pentz
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada.
authors.forename: Palma
authors.initials: P
authors.lastname: Gubert
authors.affiliation: IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.affiliation: ANFFAS-Catania, Catania, Italy.
authors.forename: Rita Anna
authors.initials: RA
authors.lastname: Cantarella
authors.affiliation: IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors.forename: Flaviana
authors.initials: F
authors.lastname: Elia
authors.affiliation: IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors.forename: Serafino
authors.initials: S
authors.lastname: Buono
authors.affiliation: IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors.forename: Marilena
authors.initials: M
authors.lastname: Recupero
authors.affiliation: IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Romano
authors.affiliation: Department of Educational Sciences, University of Catania, Catania, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Castellano
authors.affiliation: IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bosco
authors.affiliation: Department of Educational Sciences, University of Catania, Catania, Italy.
authors.forename: Santo
authors.initials: S
authors.lastname: Di Nuovo
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Drago
authors.affiliation: IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy; Department of Drug Sciences, University of Catania, Catania, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Caraci
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada; Department of Neurology and Neurosurgery, McGill University, Montreal, Canada; Department of Anatomy and Cell Biology, McGill University, Montreal, Canada. Electronic address: claudio.cuello@mcgill.ca.
authors.forename: A Claudio
authors.initials: AC
authors.lastname: Cuello
mesh_terms: D000293:Adolescent; D000328:Adult; D016229:Amyloid beta-Peptides / Q000097:blood; D015415:Biomarkers / Q000097:blood; D060825:Cognitive Dysfunction / Q000097:blood / Q000209:etiology / Q000276:immunology; D016207:Cytokines / Q000097:blood; D018450:Disease Progression; D004314:Down Syndrome / Q000097:blood* / Q000276:immunology* / Q000523:psychology; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000097:blood; D009479:Neuropeptides / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D015843:Serpins / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D055815:Young Adult; D000097522:Neuroserpin
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D016207:Cytokines; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020932:Nerve Growth Factor; D009479:Neuropeptides; D010446:Peptide Fragments; D011498:Protein Precursors; D015843:Serpins; D010959:Tissue Plasminogen Activator; D000097522:Neuroserpin; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); C061397:pro-nerve growth factor, human; C511768:MMP3 protein, human; C579270:MMP9 protein, human
keywords: Alzheimer's disease; Amyloid-β; Biomarker; Blood; Down syndrome; Inflammation; MMP-3; MMP-9; Metallo-proteases; Nerve growth factor; Plasma; proNGF