S-Adenosylhomocysteine: A Better Marker of the Development of Alzheimer's Disease than Homocysteine?

Abstract

The article by Popp and colleagues [1] highlights the association between the alteration in homocysteine metabolism and Alzheimer's disease (AD) pathology (as reflected by the cerebrospinal fluid biomarkers amyloid-β 1−42 and P-tau181). Moreover, they raise the question as to whether S-adenosylhomocysteine (SAH) is a better marker of the development of AD than homocysteine. Although Popp and colleagues [1] found that phosphorylated tau was strongly associated with SAH rather than homocysteine, they did not study the mechanism underlying the SAH-AD association. The data from clinical and epidemiologic studies do not consistently show that plasma levels of homocysteine are associated with an increased risk of cognitive impairment and AD [2][3][4]. Similarly, clinical trials of vitamin B supplementation as a means of lowering homocysteine levels to prevent cognitive decline in AD patients have not been consistently successful [5,6] increasing evidence indicates that high plasma levels of homocysteine may not be a marker of vascular injury [6], the finding by Popp and colleagues that SAH, not homocysteine, is associated with tau accumulation in AD patients is not surprising.Vascular injury is an essential component underlying both AD and cognitive impairment in the elderly. The relationship between hyperhomocysteinemia and vascular disease is somewhat controversial. Increasing data suggest SAH is a better indicator of cardiovascular disease and atherosclerosis than is homocysteine [7,8]. In neurodegenerative diseases, elevated homocysteine levels can lead to higher brain levels of SAH and, in turn, increase phosphorylation of tau [9], supporting the crucial role of SAH in the development of AD. Despite the strong association of increased SAH and tau in AD patients, the molecular mechanisms of SAH-induced neuronal injury (which are most likely vascular) are not clear [7,8]. We have recently studied the mechanisms involved in vascular damage induced by homocysteine and SAH [10].In our study, exposure of human coronary artery endothelial cells to homocysteine alone, even at supra-

One-carbon metabolism, cognitive impairment and CSF measures of Alzheimer pathology: homocysteine and beyond

“…However, we observed higher CSF choline in cognitive impairment, an inconsistency that may reflect neurodegeneration and the breakdown of synaptic membranes enriched with choline [42]. We showed significantly increased CSF and plasma SAH in cognitive impairment, which is consistent with previous findings [14, 43]. …”