Inflammation profiles in Alzheimer's disease relate to cognition and neurodegeneration
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Abstract 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. alz71642-sec-0010 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. alz71642-sec-0020 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). alz71642-sec-0030 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. alz71642-sec-0040 Highlights Data‐driven cytokine profiles differ between patients with Alzheimer's disease and healthy participants. Pro‐inflammatory signatures are elevated
Abstract
Abstract 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. alz71642-sec-0010 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. alz71642-sec-0020 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). alz71642-sec-0030 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. alz71642-sec-0040 Highlights Data‐driven cytokine profiles differ between patients with Alzheimer's disease and healthy participants. Pro‐inflammatory signatures are elevated in Black/African American individuals relative to White and Asian participants. Plasma phosphorylated tau 217 (p‐tau217) is not associated with inflammatory signatures. Neurofilament light (NfL) mediates pro‐inflammatory profile's effects on cognition. bullet alz71642-list-0001 highlights