S-adenosylmethionine and S-adenosylhomocysteine levels in the aging brain of APP/PS1 Alzheimer mice

Hyperhomocysteinemia and factors of homocysteine metabolism, S-adenosylhomocysteine (AdoHcy) and S-adenosylmethionine (AdoMet), may play a role in Alzheimer’s disease (AD). With liquid-chromatography-tandem-mass-spectrometry AdoMet and AdoHcy were determined in brains of 8- and 15-month-old APP/PS1 Alzheimer mice, and their possible roles in AD brains investigated. The finding that AdoMet levels do not differ between the genotypes in (young) 8-month-old mice, but are different in (older) 15-month-old APP/PS1 mice compared to their wild-type littermates, suggests that alterations in AdoMet are a consequence of AD pathology rather than a cause. During aging, AdoMet levels decreased in the brains of wild-type mice, whereas AdoHcy levels diminished in both wild type and APP/PS1 mice. The finding that AdoMet levels in APP/PS1 mice are not decreased during aging (in contrast to wild-type mice), is probably related to less demand due to neurodegeneration. No effect of the omega-3 fatty acid docosahexaenoic acid (DHA) or cholesterol-enriched diets on AdoMet or AdoHcy levels were found

Catechol-O-Methyltransferase (COMT) Val(108/158 )Met polymorphism does not modulate executive function in children with ADHD

BACKGROUND: An association has been observed between the catechol-O-methyltransferase (COMT) gene, the predominant means of catecholamine catabolism within the prefrontal cortex (PFC), and neuropsychological task performance in healthy and schizophrenic adults. Since several of the cognitive functions typically deficient in children with Attention Deficit Hyperactivity Disorder (ADHD) are mediated by prefrontal dopamine (DA) mechanisms, we investigated the relationship between a functional polymorphism of the COMT gene and neuropsychological task performance in these children. METHODS: The Val(108/158 )Met polymorphism of the COMT gene was genotyped in 118 children with ADHD (DSM-IV). The Wisconsin Card Sorting Test (WCST), Tower of London (TOL), and Self-Ordered Pointing Task (SOPT) were employed to evaluate executive functions. Neuropsychological task performance was compared across genotype groups using analysis of variance. RESULTS: ADHD children with the Val/Val, Val/Met and Met/Met genotypes were similar with regard to demographic and clinical characteristics. No genotype effects were observed for WCST standardized perseverative error scores [F(2,97 )= 0.67; p > 0.05], TOL standardized scores [F(2,99 )= 0.97; p > 0.05], and SOPT error scores [F(2,108 )= 0.62; p > 0.05]. CONCLUSIONS: Contrary to the observed association between WCST performance and the Val(108/158 )Met polymorphism of the COMT gene in both healthy and schizophrenic adults, this polymorphism does not appear to modulate executive functions in children with ADHD