Year: 2020
Type: article
Study design: Observational Study
Abstract: 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.
Source: PLoS ONE
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,695
Awards: UC Davis Alzheimer's Disease Core Center, G1353455142, G1632916191, Novel imaging and endothelial biomarkers of small vessel cerebrovascular disease, G1888650583, The role of IL-17B/CXCL5 in metabolic syndrome-induced white matter stroke, G343469054, G36433118, ADSP Follow-up in Multi-Ethnic Cohorts via Endophenotypes, Omics & Model Systems, Do Atmospheric Ultrafine Particles Lodge in the Brain and Cause Cognitive Decline Leading to Alzheimer's Disease Related Dementias?, G4684857399, G4740807435, G6348851466, G7216933433, G76412088, G7939065199, G816726602, Characterization of lipid biomarkers in the detection, prognosis, and time course of acute ischemic stroke, G9000108235, G9000265646, G9000353542, UCLA Medical Student Training in Aging Research (MSTAR) Program
OpenAlex ID: W3003088065