Network-level organization of systemic inflammation reflects early Alzheimer’s-like behavioral changes
Year: 2025
Type: article
Abstract: Systemic immune alterations are increasingly recognized as features of Alzheimer's disease (AD), yet their network-level organization in preclinical models is poorly understood. We profiled 66 circulating cytokines and growth factors in young adult TgF344-AD and wild-type rats, reduced the data into five inflammatory profiles via principal component analysis, and mapped these profiles onto protein-protein interaction networks. Multivariate analyses revealed genotype- and sex-dependent network organization, with distinct modules enriched for extracellular matrix-linked interleukin signaling or systemic pro-inflammatory cytokine receptor signaling. Regression analyses controlling for genotype and sex linked these networks to specific behavioral domains: extracellular matrix-associated interleukins predicted altered intertemporal choice, whereas pro-inflammatory cytokine receptor signaling correlated with reduced motivation. These findings provide evidence consistent with systemic inflammatory network remodeling at prodromal stages in a preclinical AD model of AD-like pathology and outline a mechanistically interpretable analytical framework with clear translational potential for integrating peripheral immune signatures with behavioral outcomes across species.
Source: Scientific Reports
Institutions: University of Alabama at Birmingham, UAB Medicine
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: Brain Research Foundation, McKnight Foundation, Evelyn F. McKnight Brain Research Foundation, National Institutes of Health, National Institute on Aging, National Institute of Child Health and Human Development, Eunice Kennedy Shriver National Institute of Child Health and Human Development
OpenAlex ID: W4417012895