Background: Patients affected by dementia Alzheimer type (DAT) or vascular dementia (VD) often exhibit mild hyperhomocysteinemia (HHcy); HHcy may be important in neuron damage: it is an early marker of vitamin deficit, (folate and vit. B12), often associated with cognitive decline; HHcy itself seems to exert a neurotoxic effect (activation of NMDA receptors and induction of cell death; excitotoxic effect by some metabolites) and it is also an indipendent risk factor for (cerebro)vascular disease. Red blood cells (RBC) have enzymatic activities for Hcy synthesis (methionine demethylation) and (probably) metabolism (remethylation to methionine), representing a possible model for studying abnormalities of Hcy metabolism.Aim: to assess the possible difference in RBC production between healthy elderly and elderly affected by Dementia syndrome.Methods: In 105 subjects affected by dementia (DSM-IV criteria) [55 by DAT (30 f, mean age 78±8 years) and 50 by VD (38 f, 81±5 years); DAT and VD diagnosis was made by NINCDS-ARDRA and NINDS-AIREN criteria and Hachinsky score] and 40 healthyelderly (controls; 22 f; mean aged 77±10 years) we assessed fasting plasma Hcy (HPLC) and serum vit. B12 and RBC folates (RIA) . A RBC sample from all subjects was incubated at 37° for 8 h in RPMI vitamin-free (Ht=26%) medium. In these samples we measured at time 0 e after 4 and 8 hour Hcy concentration (supernatant and RBC cytoplasm).Results: RBC from AD patients produce more Hcy (p<0.05 for all parameters in DAT e VD vs. controls, ANOVA, Tukey post hoc); in RBC from VD patients Hcy production is higher than from DAT, but not significantly (p=0.055) (see figure). Data are corrected for Hcy-related vitamin status.Conclusions: Our data are suggestive that AD patients have higher prevalence of transmethylathion abnormalities with respect to controls. This may have both indirect (role of methylation in normal neuron trophism) and direct (toxicity due to Hcy accumulation) physiologic relevance.
Homocysteine erythrocyte production in patients affected by dementia / Ventura, Paolo; Panini, Rossana; M., Uneddu; M., Modugno; Neri, Mirco; Salvioli, Gianfranco. - STAMPA. - 1:(2001), pp. 137-137. (Intervento presentato al convegno Homocysteine Metabolism 3rd International Conference tenutosi a Sorrento - Italy nel 1-5 July 2001).
Homocysteine erythrocyte production in patients affected by dementia
VENTURA, Paolo;PANINI, Rossana;NERI, Mirco;SALVIOLI, Gianfranco
2001
Abstract
Background: Patients affected by dementia Alzheimer type (DAT) or vascular dementia (VD) often exhibit mild hyperhomocysteinemia (HHcy); HHcy may be important in neuron damage: it is an early marker of vitamin deficit, (folate and vit. B12), often associated with cognitive decline; HHcy itself seems to exert a neurotoxic effect (activation of NMDA receptors and induction of cell death; excitotoxic effect by some metabolites) and it is also an indipendent risk factor for (cerebro)vascular disease. Red blood cells (RBC) have enzymatic activities for Hcy synthesis (methionine demethylation) and (probably) metabolism (remethylation to methionine), representing a possible model for studying abnormalities of Hcy metabolism.Aim: to assess the possible difference in RBC production between healthy elderly and elderly affected by Dementia syndrome.Methods: In 105 subjects affected by dementia (DSM-IV criteria) [55 by DAT (30 f, mean age 78±8 years) and 50 by VD (38 f, 81±5 years); DAT and VD diagnosis was made by NINCDS-ARDRA and NINDS-AIREN criteria and Hachinsky score] and 40 healthyelderly (controls; 22 f; mean aged 77±10 years) we assessed fasting plasma Hcy (HPLC) and serum vit. B12 and RBC folates (RIA) . A RBC sample from all subjects was incubated at 37° for 8 h in RPMI vitamin-free (Ht=26%) medium. In these samples we measured at time 0 e after 4 and 8 hour Hcy concentration (supernatant and RBC cytoplasm).Results: RBC from AD patients produce more Hcy (p<0.05 for all parameters in DAT e VD vs. controls, ANOVA, Tukey post hoc); in RBC from VD patients Hcy production is higher than from DAT, but not significantly (p=0.055) (see figure). Data are corrected for Hcy-related vitamin status.Conclusions: Our data are suggestive that AD patients have higher prevalence of transmethylathion abnormalities with respect to controls. This may have both indirect (role of methylation in normal neuron trophism) and direct (toxicity due to Hcy accumulation) physiologic relevance.
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