Inflammation profiles in Alzheimer's disease relate to cognition and neurodegeneration
Katherine R. Birditt, Kalliopi Mavromati, Peter Swann, Terence Quinn, Atticus H. Hainsworth, Lynne Hughes, John T. O'Brien, William McEwan, Maura MalpettiAbstract
INTRODUCTION
Immune signaling alterations have been implicated in Alzheimer's disease (AD) pathophysiology, but their heterogeneity across the disease continuum in real‐world cohorts is poorly characterized, limiting the development of stratified immunomodulatory approaches.
METHODS
In a diverse multicenter cohort (BioHermes) of 176 amyloid‐positive individuals with AD/mild cognitive impairment (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 neurofilament light [NfL], phosphorylated tau 217 [p‐tau217], and glial fibrillary acidic protein [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.