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Plasma biomarkers for amyloid, tau, and cytokines in Down syndrome and sporadic Alzheimer’s disease

Startin, Carla, Ashton, Nicholas J., Hamburg, Sarah, Hithersay, Rosalyn, Wiseman, Frances K., Mok, Kin Y., Hardy, John, Lleó, Alberto, Lovestone, Simon, Parnetti, Lucilla , Zetterberg, Henrik, Hye, Abdul and Strydom, André (2019) Plasma biomarkers for amyloid, tau, and cytokines in Down syndrome and sporadic Alzheimer’s disease Alzheimer's Research & Therapy, 11 (26).

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Abstract

Background: Down syndrome (DS), caused by chromosome 21 trisomy, is associated with an ultra-high risk of dementia due to Alzheimer’s disease (AD), driven by amyloid precursor protein (APP) gene triplication. Understanding relevant molecular differences between those with DS, those with sporadic AD (sAD) without DS, and controls will aid in understanding AD development in DS. We explored group differences in plasma concentrations of amyloid-β peptides and tau (as their accumulation is a characteristic feature of AD) and cytokines (as the inflammatory response has been implicated in AD development, and immune dysfunction is common in DS). Methods: We used ultrasensitive assays to compare plasma concentrations of the amyloid-β peptides Aβ40 and Aβ42, total tau (t-tau), and the cytokines IL1β, IL10, IL6, and TNFα between adults with DS (n = 31), adults with sAD (n = 27), and controls age-matched to the group with DS (n = 27), and explored relationships between molecular concentrations and with age within each group. In the group with DS, we also explored relationships with neurofilament light (NfL) concentration, due to its potential use as a biomarker for AD in DS. Results: Aβ40, Aβ42, and IL1β concentrations were higher in DS, with a higher Aβ42/Aβ40 ratio in controls. The group with DS showed moderate positive associations between concentrations of t-tau and both Aβ42 and IL1β. Only NfL concentration in the group with DS showed a significant positive association with age. Conclusions: Concentrations of Aβ40 and Aβ42 were much higher in adults with DS than in other groups, reflecting APP gene triplication, while no difference in the Aβ42/Aβ40 ratio between those with DS and sAD may indicate similar processing and deposition of Aβ40 and Aβ42 in these groups. Higher concentrations of IL1β in DS may reflect an increased vulnerability to infections and/or an increased prevalence of autoimmune disorders, while the positive association between IL1β and t-tau in DS may indicate IL1β is associated with neurodegeneration. Finally, NfL concentration may be the most suitable biomarker for dementia progression in DS. The identification of such a biomarker is important to improve the detection of dementia and monitor its progression, and for designing clinical intervention studies.

Item Type: Article
Divisions : Faculty of Health and Medical Sciences > School of Psychology
Authors :
NameEmailORCID
Startin, Carlac.startin@surrey.ac.uk
Ashton, Nicholas J.
Hamburg, Sarah
Hithersay, Rosalyn
Wiseman, Frances K.
Mok, Kin Y.
Hardy, John
Lleó, Alberto
Lovestone, Simon
Parnetti, Lucilla
Zetterberg, Henrik
Hye, Abdul
Strydom, André
Date : 21 March 2019
Funders : Wellcome Trust Strategic Award, UCL ARUK network, Baily Thomas Charitable Fund
DOI : 10.1186/s13195-019-0477-0
Copyright Disclaimer : © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Uncontrolled Keywords : Down syndrome; Alzheimer’s disease; Dementia; Biomarker; Plasma; Amyloid; Tau; Interleukin 1β; Cytokines
Depositing User : Diane Maxfield
Date Deposited : 04 Apr 2019 15:42
Last Modified : 04 Apr 2019 15:42
URI: http://epubs.surrey.ac.uk/id/eprint/850971

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