Inflammation Associated With Obesity, Aging, and Amyloid Burden in Adults With Down Syndrome

Abstract

Objective: Adults with Down syndrome (DS) often show elevated systemic inflammation, but the association with obesity, aging, and Alzheimer's disease (AD) pathology is not well understood.

Methods: Data were drawn from 188 nondemented adults with DS participating in the Alzheimer Biomarkers Consortium-DS (ABC-DS). Participants completed clinical assessments, blood draws, and neuroimaging. Plasma biomarkers included indicators of general, pro-, and anti-inflammation. Mixed linear models tested associations between BMI, age, PET-measured amyloid burden, and inflammatory biomarkers, adjusting for sex, trisomy type, and collection site. False discovery rate correction was applied.

Results: The majority of the participants met criteria for obesity. Higher BMI was significantly associated with elevated levels of CRP, IL-6, TNF-α, B2M, IL-18, and slCAM-1 (p < 0.05). Older age was significantly associated with higher B2M (β = 1.22e + 05, p < 0.001). Amyloid burden was positively associated with IL-6 (β = 0.005, p = 0.037).

Conclusions: Obesity, aging, and amyloid burden relate to systemic inflammation in adults with DS. Obesity showed the strongest and most consistent associations, emphasizing the value of regular monitoring and weight management strategies to help reduce inflammation. Aging and early amyloid accumulation showed more limited links with systemic inflammation; future work should examine whether these processes are more closely related to biomarkers of neuroinflammation as AD progresses.