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Meta-Analysis
. 2019 Jul;79(7):684-698.
doi: 10.1002/dneu.22715. Epub 2019 Sep 11.

Plasma amyloid and tau as dementia biomarkers in Down syndrome: Systematic review and meta-analyses

Falah Alhajraf  1   2 , Deborah Ness  3   4 , Abdul Hye  5 , Andre Strydom  3   4
Affiliations
Meta-Analysis

Plasma amyloid and tau as dementia biomarkers in Down syndrome: Systematic review and meta-analyses

Falah Alhajraf et al. Dev Neurobiol. 2019 Jul.

Abstract

Individuals with Down syndrome (DS) are at high risk of developing Alzheimer's disease (AD). Discovering reliable biomarkers which could facilitate early AD diagnosis and be used to predict/monitor disease course would be extremely valuable. To examine if analytes in blood related to amyloid plaques may constitute such biomarkers, we conducted meta-analyses of studies comparing plasma amyloid beta (Aβ) levels between DS individuals and controls, and between DS individuals with and without dementia. PubMed, Embase, and Google Scholar were searched for studies investigating the relationship between Aβ plasma concentrations and dementia in DS and 10 studies collectively comprising >1,600 adults, including >1,400 individuals with DS, were included. RevMan 5.3 was used to perform meta-analyses. Meta-analyses showed higher plasma Aβ40 (SMD = 1.79, 95% CI [1.14, 2.44], Z = 5.40, p < .00001) and plasma Aβ42 levels (SMD = 1.41, 95% CI [1.15, 1.68], Z = 10.46, p < .00001) in DS individuals than controls, and revealed that DS individuals with dementia had higher plasma Aβ40 levels (SMD = 0.23, 95% CI [0.05, 0.41], Z = 2.54, p = .01) and lower Aβ42 /Aβ40 ratios (SMD = -0.33, 95% CI [-0.63, -0.03], Z = 2.15, p = .03) than DS individuals without dementia. Our results indicate that plasma Aβ40 levels may constitute a promising biomarker for predicting dementia status in individuals with DS. Further investigations using new ultra-sensitive assays are required to obtain more reliable results and to investigate to what extent these results may be generalizable beyond the DS population.

Keywords: Alzheimer's disease; Down syndrome; biomarkers; dementia; plasma/blood amyloid/Aβ.

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Conflict of interest statement

All authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Flow chart diagram of study selection and inclusion
Figure 2
Figure 2
Meta‐analysis of studies comparing plasma Aβ40 levels of individuals with DS and healthy controls. Abbreviations: DS = Down syndrome, SD = standard deviation, CI = Confidence Interval, Std. = Standardized [Color figure can be viewed at http://www.wileyonlinelibrary.com]
Figure 3
Figure 3
Meta‐analysis of studies comparing plasma Aβ42 levels of individuals with DS and healthy controls. Abbreviations: DS = Down syndrome, SD = standard deviation, CI = Confidence Interval, Std. = Standardized [Color figure can be viewed at http://www.wileyonlinelibrary.com]
Figure 4
Figure 4
Meta‐analysis of studies comparing plasma Aβ40 levels of DS individuals with and without dementia. Abbreviations: DS = Down syndrome, SD = standard deviation, CI = Confidence Interval, Std. = Standardized [Color figure can be viewed at http://www.wileyonlinelibrary.com]
Figure 5
Figure 5
Meta‐analysis of studies comparing plasma Aβ42 levels of DS individuals with and without dementia. Abbreviations: DS = Down syndrome, SD = standard deviation, CI = Confidence Interval, Std. = Standardized [Color figure can be viewed at http://www.wileyonlinelibrary.com]
Figure 6
Figure 6
Meta‐analysis of studies comparing plasma Aβ42/Aβ40 ratios of DS individuals with and without dementia. Abbreviations: DS = Down syndrome, SD = standard deviation, CI = Confidence Interval, Std. = Standardized [Color figure can be viewed at http://www.wileyonlinelibrary.com]
See this image and copyright information in PMC

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