title: Homocysteine, folate deprivation and Alzheimer neuropathology.
abstract: Increased levels of homocysteine (HC), arising in some situations via deficiencies in folate--an essential cofactor in metabolic regulation of HC--have long been known to contribute to cardiovascular disorders and stroke. More recently, clinical studies implicate increased HC and reduced folate with neurodegenerative conditions including Alzheimer's disease. It has remained unclear from clinical studies whether the neurotoxicity of increased HC and/or reduced folate is derived from direct detrimental effects on neurons themselves, or is instead derived indirectly following perturbation of nervous system vasculature. However, recent reports from several laboratories provide evidence that HC not only induces direct neurotoxicity, but also potentiates both amyloid-beta and glutamate neurotoxicity. These latter studies leave open the possibility that even mild elevations in HC may place neurons at risk for additional trauma. The potential contribution of folate deficiency and resultant increases in HC to neurodegeneration in AD, and therapeutic approaches to alleviate their impact, is discussed.
authors.affiliation: Center for Cellular Neurobiology and Neurodegeneration Research, Department of Biological Sciences, Department of Health and Clinical Sciences, Department of Biochemistry, UMass, Lowell, Lowell, MA 01854, USA.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Shea
authors.forename: James
authors.initials: J
authors.lastname: Lyons-Weiler
authors.forename: Eugene
authors.initials: E
authors.lastname: Rogers
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology; D005494:Folic Acid Deficiency / Q000473:pathology*; D006710:Homocysteine / Q000378:metabolism*; D006801:Humans; D008715:Methionine / Q000378:metabolism; D009410:Nerve Degeneration / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D006710:Homocysteine; D008715:Methionine