W157 - Segregating the Regional Effects of Aging and Blood Immune Factors on Age Related Brain Athrophy

Immunology and neuroscience are historically distant fields with limited intercommunication partially justified by the observation that the brain blood barrier keeps the brain isolated while microglia provide its immune defense. The newly developing science of aging has revealed that the chronic presence of proinflammatory immune factors has effects on accelerating the aging process in multiple tissues including the central nervous system. Noninvasive volumetric MRI scans have identified the loss of brain volume as a hallmark of the aging brain. Here we study a cohort of 554 subjects using structural MRI scans and blood immune proteins concentrations. We identify a set of age predictive proteins whose concentrations change with age (TNF_l, IL-6, MCP-1, IP-10, Eotaxin, VEGF-D, VEGF, PLGF and Vcam-1). From these we extract a cytokine clock (CyClo) that can estimate the subject age (±6 years). The proteins with the highest contributions to the clock are known for roles in vascular growth (VEGF, VEGF-D and PLGF), general levels of inflammation (TNF_l, IL-6), chemoattraction for monocytes/macrophages (MCP-1, IP-10), recruitment of eosinophils into sites of inflammation (Eotaxin) and promote the interaction between vasculature and immune cells (Vcam-1).  Using machine learning we correlate the variance in volume of multiple functionally determined cortical networks with the age, sex and CyClo of our subjects. We find that the variability in volume of the different networks and these three factors associate differentially thus suggesting targeted vulnerabilities of certain functional networks (default mode, limbic, dorsal attention network) to circulating levels of immune markers of aging and chronic inflammation.