Structured Abstract Introduction Immune signalling alterations have been implicated in Alzheimer’s disease (AD) pathophysiology, but their heterogeneity across the disease continuum in real-world cohorts is poorly characterised, limiting the development of stratified immunomodulatory approaches. Methods In a diverse multicentre cohort (BioHermes) of 176 amyloid-positive individuals with AD/MCI and 173 age and sex-matched controls, principal component analysis was performed on Luminex-measured plasma cytokines to derive inflammatory signatures, and their direct/indirect associations with cognition and neurodegeneration. Results Two components were identified. Proinflammatory Component 2 was elevated in AD/MCI and in Black/African American participants and strongly associated with poorer cognition (independently of NfL, ptau217 and GFAP). Inflammatory Component 1 showed an indirect association with cognition, mediated by neurodegeneration (plasma NfL). Discussion Plasma inflammation profiles were associated with poorer cognition via direct and neurodegeneration-mediated pathways, supporting their potential use as stratification markers in AD therapeutics.
Malpetti et al. (Sat,) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: