Plasma hydrogen sulfide: A biomarker of Alzheimer's disease and related dementias

Abstract

While heart disease remains a common cause of mortality, cerebrovascular disease also increases with age, and has been implicated in Alzheimer's disease and related dementias (ADRD). We have described hydrogen sulfide (H₂S), a signaling molecule important in vascular homeostasis, as a biomarker of cardiovascular disease. We hypothesize that plasma H₂S and its metabolites also relate to vascular and cognitive dysfunction in ADRD. We used analytical biochemical methods to measure plasma H₂S metabolites and MRI to evaluate indicators of microvascular disease in ADRD. Levels of total H₂S and specific metabolites were increased in ADRD versus controls. Cognition and microvascular disease indices were correlated with H₂S levels. Total plasma sulfide was the strongest indicator of ADRD, and partially drove the relationship between cognitive dysfunction and white matter lesion volume, an indicator of microvascular disease. Our findings show that H₂S is dysregulated in dementia, providing a potential biomarker for diagnosis and intervention.