However, diet-induced high Hcy resulted in a significant increase in Aβ, tau phosphorylation, neuroinflammation, synaptic pathology and memory impairment in control mice, but not in mice lacking ALOX5.Taken together our findings demonstrate that the up-regulation of the ALOX5 gene pathway is responsible for the development of the biochemical and behavioral sequelae of high Hcy brain levels in the context of a neurodegenerative phenotype.