Biomarkers

Background: Down syndrome (DS) is a genetic disorder characterized by trisomy 21, which is linked to molecular alterations, such as neuroinflammation and accumulation of amyloid-beta (Ab) peptide that can cause early-onset Alzheimer's disease (AD). This study aims to evaluate the presence of neuroinflammation in individuals with DS in different ages and the association with Ab plaques.

Methods: Age-matched DS (n=24) and non-DS individuals (n=15) underwent two hybrid PET/MRI acquisition for neuroinflammation and Ab burden assessment using [¹¹C]PK11195 (∼370 MBq and 60 min acquisition) and [¹¹C]PIB (∼370 MBq and 70 min acquisition) tracers, respectively. Quantification is presented as standard uptake values (SUV 40-60min) for [¹¹C]PK11195 (PMOD software) and SUVratio (SUVr 50-70 min) for [¹¹C]PIB using cerebellum grey matter as reference tissue (CortexID software) and cortical areas as a unique VOI called "composite". Statistical analyses were performed dividing the DS group in <40 (n=13) and ≥40 (n=11) years of age. Differences in [¹¹C]PK11195-SUV and [¹¹C]PIB-SUVr were assessed by applying a multivariate one-way ANOVA test with Bonferroni analysis for multiple comparisons. Correlation analyses were applied between [¹¹C]PK11195-SUV, [¹¹C]PIB-SUVr, and age variables.

Results: Significant higher [11C]PK11195-SUV was found in the occipital lobe (p<0.001), temporal lobe (p<0.001), and cingulum posterior (p<0.0001) when comparing the older to younger DS groups. Significant [¹¹C]PIB-SUVr differences were found for all groups, with the DS≥40 group showing the highest [11C]PIB uptake, followed by the DS<40 and non-DS groups. No correlations were found between [¹¹C]PK11195 and [¹¹C]PIB measurements. However, for DS individuals, positive significant correlations with age was observed for [¹¹C]PK11195-SUV in the occipital lobe (p<0.05), temporal lobe (p<0.01), cingulum posterior (p<0.001), hippocampus (p<0.05), amygdala (p<0.05), striatum (p<0.05), and cerebellum (p<0.05), and for [11C]PIB-SUVr in the composite VOI (p<0.01).

Conclusion: [¹¹C]PK11195-PET analysis suggests increased neuroinflammation in older DS subjects. [¹¹C]PIB-PET results show a higher Ab burden in DS≥40 individuals and early accumulation of Ab in DS<40 individuals in comparison to non-DS age-matched subjects. More in-vivo studies are needed to understand the temporal relationship between neuroinflammation and Ab deposition in the brain of individuals with DS.