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

Journal article
Authors C. M. Startin
Nicholas Ashton
S. Hamburg
R. Hithersay
F. K. Wiseman
K. Y. Mok
J. Hardy
A. Lleo
S. Lovestone
L. Parnetti
Henrik Zetterberg
A. Hye
E. Fisher
D. Nizetic
J. Hardy
R. L. Weston
V. Tybulewicz
A. Karmiloff-Smith
A. Strydom
Ajmg V. P. Vani S
Published in Alzheimers Research & Therapy
Volume 11
ISSN 1758-9193
Publication year 2019
Published at Wallenberg Laboratory
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Language en
Links dx.doi.org/10.1186/s13195-019-0477-...
Keywords Down syndrome, Alzheimer's disease, Dementia, Biomarker, Plasma, Amyloid, Tau, Interleukin 1, Cytokines, cognitive decline, inflammatory cytokines, neurofilament light, beta, concentrations, follow-up, dementia, children, adults, association, risk, Neurosciences & Neurology, khann g, 1984, neurology, v34, p939
Subject categories Neurosciences

Abstract

BackgroundDown 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- 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).MethodsWe used ultrasensitive assays to compare plasma concentrations of the amyloid- peptides A(40) and A(42), total tau (t-tau), and the cytokines IL1, IL10, IL6, and TNF 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.ResultsA(40), A(42), and IL1 concentrations were higher in DS, with a higher A(42)/A(40) ratio in controls. The group with DS showed moderate positive associations between concentrations of t-tau and both A(42) and IL1. Only NfL concentration in the group with DS showed a significant positive association with age.ConclusionsConcentrations of A(40) and A(42) were much higher in adults with DS than in other groups, reflecting APP gene triplication, while no difference in the A(42)/A(40) ratio between those with DS and sAD may indicate similar processing and deposition of A(40) and A(42) in these groups. Higher concentrations of IL1 in DS may reflect an increased vulnerability to infections and/or an increased prevalence of autoimmune disorders, while the positive association between IL1 and t-tau in DS may indicate IL1 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.

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