title: Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer's Disease.
abstract: Alzheimer's disease (AD) is the major cause of dementia and no preventive or effective treatment has been established to date. The etiology of AD is poorly understood, but genetic and environmental factors seem to play a role in its onset and progression. In particular, factors affecting the one-carbon metabolism (OCM) are thought to be important and elevated homocysteine (Hcy) levels, indicating impaired OCM, have been associated with AD. We aimed at evaluating the role of polymorphisms of key OCM enzymes in the etiology of AD, particularly when intakes of relevant B-vitamins are inadequate. Our review indicates that a range of compensatory mechanisms exist to maintain a metabolic balance. However, these become overwhelmed if the activity of more than one enzyme is reduced due to genetic factors or insufficient folate, riboflavin, vitamin B6 and/or vitamin B12 levels. Consequences include increased Hcy levels and reduced capacity to synthetize, methylate and repair DNA, and/or modulated neurotransmission. This seems to favor the development of hallmarks of AD particularly when combined with increased oxidative stress e.g., in apolipoprotein E (ApoE) ε4 carriers. However, as these effects can be compensated at least partially by adequate intakes of B-vitamins, achieving optimal B-vitamin status for the general population should be a public health priority.
authors.affiliation: DSM Nutritional Products Ltd., Wurmisweg 576, Kaiseraugst 4303, Switzerland. barbara.troesch@dsm.com.
authors.forename: Barbara
authors.initials: B
authors.lastname: Troesch
authors.affiliation: DSM Nutritional Products Ltd., Wurmisweg 576, Kaiseraugst 4303, Switzerland. peter.weber@dsm.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Weber
authors.affiliation: DSM Nutritional Products Ltd., Wurmisweg 576, Kaiseraugst 4303, Switzerland. hasan.mohajeri@dsm.com.
authors.forename: M Hasan
authors.initials: MH
authors.lastname: Mohajeri
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics / Q000378:metabolism; D000544:Alzheimer Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D000818:Animals; D003541:Cystathionine beta-Synthase / Q000235:genetics / Q000378:metabolism; D019317:Evidence-Based Medicine; D005287:Ferredoxin-NADP Reductase / Q000235:genetics / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020138:Hyperhomocysteinemia / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D008715:Methionine / Q000378:metabolism*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D016254:Mutagenesis, Insertional; D054647:Nutrigenomics / Q000379:methods / Q000639:trends; D009752:Nutritional Status; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D020080:Tandem Repeat Sequences; D014803:Vitamin B Complex / Q000378:metabolism / Q000627:therapeutic use; D014804:Vitamin B Deficiency / Q000178:diet therapy / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control
chemical_list: D014803:Vitamin B Complex; D008715:Methionine; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; C585801:MTR protein, human; D012696:Glycine Hydroxymethyltransferase; C520541:SHMT protein, human; D003541:Cystathionine beta-Synthase
keywords: Alzheimer’s disease; B-vitamins; dementia; homocysteine; nutrition; one-carbon metabolism; polymorphism; prevention; therapy