FLUID BIOMARKERS OF PERIPHERAL AND CENTRAL INFLAMMATION OVER THE ALZHEIMER’S DISEASE CONTINUUM IN ADULTS WITH DOWN SYNDROME AND SPORADIC ALZHEIMER’S DISEASE

Adults with Down syndrome (DS) almost universally progress along the Alzheimer’s disease (AD) continuum, yet the relative contributions of trisomy 21–driven immune dysregulation versus AD-related neuroinflammation remain unclear. Here we report a cross-sectional study of 92 inflammation proteins in cerebrospinal fluid (CSF) and plasma from adults with DS or sporadic AD (sAD) and cognitively unimpaired controls (n=359) and a longitudinal study of two representative markers in CSF and plasma from adults with DS and controls (n=40).
We quantified 92 inflammatory protein proteins using the Olink Target 96 inflammation panel. CXCL9 and MMP-10 were also quantified using the Meso Scale Discovery platform. We performed linear regression for group comparisons and Spearman’s method for correlations. We controlled the false discovery rate (FDR) using the Benjamini-Hochberg method.
Adults with DS exhibited elevated inflammation proteins in plasma, prior to AD symptom onset. CSF inflammatory proteins were reduced prior to symptom onset but elevated across the AD continuum, overlapping with changes in sAD. CXCL9 and MMP-10 were selected as representative markers and taken forward for further evaluation. We observed good concordance between measures on both platforms. Longitudinally, CSF MMP10 but not CXCL9 increased with age and AD stage and correlated with AD pathophysiological biomarkers.
These data support a chronic Trisomy-21 related inflammatory state in the periphery that may be exacerbated by an AD-related proinflammatory phenotype in the central nervous system that can be measured by increasing CSF MMP-10 levels.