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Background Air pollution is associated with increased risks of vascular dementia and Alzheimer’s disease. Preexisting cerebrovascular pathologies increase susceptibility to the negatives effects of air pollution derived particulate matter, with white matter showing earlier signs of vulnerability. Epigallocatechin-3-gallate (EGCG), a polyphenol present in green tea extract, has been shown to block myelin-associated inhibitors of neurite regeneration. This study evaluates EGCG as a therapeutic strategy against white matter damage.Methods Mice (C57BL/6J) were exposed to 8 weeks (200h) of diesel exhaust particles (DEP) (100mg/m 3) or filtered air (FA) for 5h per day, 5 days a week. We included 8-weeks old male and female mice (n=4/sex/group). We induced chronic cerebral hypoperfusion (CCH) via bilateral carotid artery stenosis (BCAS) surgery four weeks before the end of the DEP/FA exposure. EGCG (20mg/kg) or vehicle (PBS) was administered orally every day following surgeries. This experiment had eight groups: FA, DEP, FA+BCAS, DEP+BCAS, FA+EGCG, DEP+EGCG, FA+BCAS+EGCG, DEP+BCAS+EGCG. White matter damage in the corpus callosum was assessed using Kluver-Barrera (KB) histology stain and SMI-312 neurofilament immunofluorescence.Results There was a significant increase in white matter damage on KB in corpus callosum in DEP (p=0.05) and DEP+BCAS (p=0.02) groups compared to FA control. EGCG markedly suppressed white matter damage on KB showing no significant difference between groups. There was a significant decrease in SMI-312 neurofilament density from FA group to: DEP group (p=0.02); Filter+BCAS (p<0.001); and DEP+BCAS (p=0.001). EGCG treatment suppressed these effects.Conclusion EGCG therapy showed potential to suppress some of the effects of white matter damage observed in the joint exposure to DEP and CCH. Consumption of green tea may be protective for white matter in a setting of air pollution exposure and vascular pathologies contributing to dementia.Disclosures M. Morales: None. K. Shkirkova: None. L. Zhao: None. S. Durra: None. S. Daggupati: None. A. Tang-Tan: None. J. Campos: None. Y. Aghaei: None. M. Mahdi Badami: None. S. Fazelvalipour: None. C. Sioutas: None. R. Gopalakrishna: None. W. Mack: None.