Brain hydrogen sulfide is severely decreased in Alzheimer's disease

Abstract Although hydrogen sulfide (H 2 S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain from cysteine by cystathionine β-synthase (CBS). H 2 S functions as a neuromodulator as well as a smooth muscle relaxant. Here we show that the levels of H 2 S are severely decreased in the brains of Alzheimer's disease (AD) patients compared with the brains of the age matched normal individuals. In addition to H 2 S production CBS also catalyzes another metabolic pathway in which cystathionine is produced from the substrate homocysteine. Previous findings, which showed that S -adenosyl- l -methionine (SAM), a CBS activator, is much reduced in AD brain and that homocysteine accumulates in the serum of AD patients, were confirmed. These observations suggest that CBS activity is reduced in AD brains and the decrease in H 2 S may be involved in some aspects of the cognitive decline in AD.