An inflammatory and trophic disconnect biomarker profile revealed in Down syndrome plasma: Relation to cognitive decline and longitudinal evaluation
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.
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The raised levels of APOE are consistent with a growing body of data indicating that the neuroimmune system differs in people with DS.
“The raised levels of APOE are consistent with a growing body of data indicating that the neuroimmune system differs in people with DS [15, 34, 46, 51, 53, 66, 67].”
From Apolipoprotein E abundance is elevated in the brains of individuals with Down syndrome–Alzheimer’s disease (2025) · cites this paper as [34]
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- Authors
- Iulita, M. F., Ower, A., Barone, C., Pentz, R., Gubert, P., Romano, C., Cantarella, R. A., Elia, F., Buono, S., Recupero, M., Romano, C., Castellano, S., Bosco, P., Di Nuovo, S., Drago, F., Caraci, F., & Cuello, A. C.
- Affiliations
- McGill University (CA)
- Imperial College London (GB)
- Oasi Maria SS (IT)
- ANFFAS‐Catania Catania Italy
- University of Catania (IT)
- Department of Educational Sciences University of Catania Catania Italy
- Corresponding author
- Cuello, A. Claudio
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2016-07-21
- Volume
- 12
- Issue
- 11
- Pages
- 1132-1148
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W2496156788
- Cited by
- 99
- References
- 104
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 10 · 2023: 2 · 2022: 7 · 2021: 12 · 2020: 18 · 2019: 15 · 2018: 8 · 2017: 9 · 2016: 1
- FWCI
- 10.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Alzheimer Society of Canada
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- Down syndrome, Alzheimer's disease
- MeSH terms
- Neuroserpin, Adolescent, Adult, Down Syndrome, Female, Humans, Longitudinal Studies, Male, Middle Aged, Neuropeptides, Peptide Fragments, Tissue Plasminogen Activator, Prospective Studies, Protein Precursors, Biomarkers, Serpins, Cytokines, Amyloid beta-Peptides, Disease Progression, Matrix Metalloproteinase 3, Matrix Metalloproteinase 9, Nerve Growth Factor, Young Adult, Cognitive Dysfunction
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