Neuroinflammation and amyloid load in different age groups of individuals with Down syndrome: A PET imaging study

Abstract

Introduction: Down syndrome (DS) is associated with early-onset Alzheimer's disease (AD). This study evaluated neuroinflammation and amyloid beta (Aβ) load in individuals with DS of different ages, using positron emission tomography (PET) imaging.

Methods: DS (n = 29) and age-matched non-DS (n = 35) individuals underwent [¹¹C]PK11195 and [¹¹C]PiB (Pittsburgh compound B) PET scans, for assessment of neuroinflammation and Aβ load, respectively. Voxel-wise and region-based analyses were conducted, and associations between [¹¹C]PK11195 binding and Aβ load were investigated.

Results: Individuals with DS exhibited increased [¹¹C]PK11195 binding compared to non-DS controls, with most pronounced differences in older (≥50 years) adults, followed by younger (20-34 years), and intermediate (35-49 years) ages. Among DS participants, 13 individuals were amyloid positive. Associations were observed between [¹¹C]PK11195 binding and global Aβ load.

Discussion: Neuroinflammation in DS follows a region-specific pattern, partially associated with amyloid deposition, and may contribute to the early progression of AD-related pathology.

Highlights: Neuroinflammation is elevated in Down syndrome (DS) versus age-matched non-DS controls. Neuroinflammation in DS shows a different pattern depending on the brain region. [¹¹C]PK11195 uptake has a positive monotonic association with amyloid burden.

Keywords: Alzheimer's disease; Down syndrome; [11C]PK11195; amyloid; neuroinflammation; positron emission tomography.