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

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 Aβ (SMD = 1.79, 95% CI [1.14, 2.44], Z = 5.40, p < .00001) and plasma Aβ 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 Aβ levels (SMD = 0.23, 95% CI [0.05, 0.41], Z = 2.54, p = .01) and lower Aβ /Aβ 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 Aβ 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.