Longitudinal plasma and CSF analyses in Down syndrome. Results from the DABNI cohort

Abstract Background Alzheimer´s disease (AD) is the main cause of death in adults with Down syndrome (DS). We describe the unique contributions of the Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) cohort by studying longitudinal changes in plasma and cerebrospinal fluid (CSF) markers. Method We included DABNI participants with DS that contributed at least two plasma and/or CSF samples and were asymptomatic (aDS, n=155), had prodromal AD (pDS, n=46) or had AD dementia (dDS; n=53) at baseline, together with 172 euploid cognitively normal controls (CN). All participants underwent longitudinal assessments, including repeated cognitive and neuropsychological assessments, plasma and CSF analyses. We applied linear‐mixed models to study changes over time in measures of GFAP, NfL and pTau217 in plasma and in AB42/AB40, NfL and pTau217 in CSF and their association with the symptomatic stages of AD. Result Plasma GFAP and NfL showed higher increases in dDS compared to pDS, and in pDS and dDS compared to aDS and CN (Figure 1A and 1B). Plasma pTau217 showed higher increases in pDS and dDS compared to aDS and CN, but there were no differences between pDS and dDS (Figure 1C). In CSF, no significant longitudinal changes were detected in AB42/AB40 (Figure 1D), whereas both NfL and pTau217 showed higher slopes in advanced symptomatic stages (Figure 1E and 1F). Conclusion Our results indicate that longitudinal changes in plasma markers are associated to different stages in the continuum of AD in DS. These changes could be useful to track the progression of the disease.