An IL-18-centered inflammatory network as a biomarker for cerebral white matter injury

Autoři: Marie Altendahl aff001;  Pauline Maillard aff002;  Danielle Harvey aff003;  Devyn Cotter aff001;  Samantha Walters aff001;  Amy Wolf aff001;  Baljeet Singh aff002;  Visesha Kakarla aff004;  Ida Azizkhanian aff005;  Sunil A. Sheth aff006;  Guanxi Xiao aff004;  Emily Fox aff001;  Michelle You aff001;  Mei Leng aff007;  David Elashoff aff007;  Joel H. Kramer aff001;  Charlie Decarli aff002;  Fanny Elahi aff001;  Jason D. Hinman aff004
Působiště autorů: Memory & Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, United States of America aff001;  Department of Neurology and Center for Neurosciences, University of California, Davis, CA, United States of America aff002;  Department of Public Health Sciences, University of California, Davis, CA, United States of America aff003;  Department of Neurology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America aff004;  School of Medicine, New York Medical College, Vahalla, NY, United States of America aff005;  University of Texas Health McGovern School of Medicine, Department of Neurology, Houston, TX, United States of America aff006;  Department of Medicine Statistics Core, Department of Medicine, University of California Los Angeles, Los Angeles, CA, United States of America aff007;  Department of Psychiatry, University of California San Francisco, San Francisco, CA, United States of America aff008
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article


Chronic systemic sterile inflammation is implicated in the pathogenesis of cerebrovascular disease and white matter injury. Non-invasive blood markers for risk stratification and dissection of inflammatory molecular substrates in vivo are lacking. We sought to identify whether an interconnected network of inflammatory biomarkers centered on IL-18 and all previously associated with white matter lesions could detect overt and antecedent white matter changes in two populations at risk for cerebral small vessel disease. In a cohort of 167 older adults (mean age: 76, SD 7.1, 83 females) that completed a cognitive battery, physical examination, and blood draw in parallel with MR imaging including DTI, we measured cerebral white matter hyperintensities (WMH) and free water (FW). Concurrently, serum levels of a biologic network of inflammation molecules including MPO, GDF-15, RAGE, ST2, IL-18, and MCP-1 were measured. The ability of a log-transformed population mean-adjusted inflammatory composite score (ICS) to associate with MR variables was demonstrated in an age and total intracranial volume adjusted model. In this cohort, ICS was significantly associated with WMH (β = 0.222, p = 0.013), FW (β = 0.3, p = 0.01), and with the number of vascular risk factor diagnoses (r = 0.36, p<0.001). In a second cohort of 131 subjects presenting for the evaluation of acute neurologic deficits concerning for stroke, we used serum levels of 11 inflammatory biomarkers in an unbiased principal component analysis which identified a single factor significantly associated with WMH. This single factor was strongly correlated with the six component ICS identified in the first cohort and was associated with WMH in a generalized linear regression model adjusted for age and gender (p = 0.027) but not acute stroke. A network of inflammatory molecules driven by IL-18 is associated with overt and antecedent white matter injury resulting from cerebrovascular disease and may be a promising peripheral biomarker for vascular white matter injury.

Klíčová slova:

Biomarkers – Central nervous system – Cognitive impairment – Diffusion tensor imaging – Inflammation – Inflammatory diseases – Magnetic resonance imaging – stroke


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