OBJECTIVE: Oxidative stress has been suggested as a contributor of Alzheimer disease (AD) neurodegeneration, particularly in those patients with late-onset AD (LOAD). Therefore, the authors studied the effect of glutathione S-transferase (GST) P1-M1-T1 gene polymorphisms and their interactions with the apolipoprotein E (ApoE) epsilon4 allelic variant on the three-year longitudinal course of AD. METHODS: Global cognitive level as measured by the Mini-Mental State Exam, basic activities of daily living (BADLs) as measured by the Physical Self-Maintenance Scale, and behavior as measured by the Neuropsychiatric Inventory, were assessed at baseline and after 1, 2, and 3 years in a sample of 99 LOAD patients. These subjects were drug naive and had undergone the first clinical examination for the diagnosis of AD. RESULTS: A multiple regression analysis indicated that the presence of ApoE epsilon4 allelic variant or GSTT1 null phenotype predicted the faster age at onset of the illness (F = 5.76, df = 2, 96, p = 0.0043). Carriers of GSTP1 *C allelic variant had a faster decline in cognitive functions (repeated measures analysis of variance [ANOVA]: F = 4.00, df = 3, 285, p = 0.008) and in BADLs (repeated measures ANOVA: F = 5.27, df = 3, 285, p = 0.001). This faster decline was independent from ApoE epsilon4 allele possession. No effect of GST P1-M1-T1 polymorphisms was found on behavioral symptom severity. CONCLUSION: These data are in line with the hypotheses that oxidative damage is a prominent feature in the clinical progression and the age at onset of LOAD.
OBJECTIVE: Oxidative stress has been suggested as a contributor of Alzheimer disease (AD) neurodegeneration, particularly in those patients with late-onset AD (LOAD). Therefore, the authors studied the effect of glutathione S-transferase (GST) P1-M1-T1 gene polymorphisms and their interactions with the apolipoprotein E (ApoE) epsilon4 allelic variant on the three-year longitudinal course of AD. METHODS: Global cognitive level as measured by the Mini-Mental State Exam, basic activities of daily living (BADLs) as measured by the Physical Self-Maintenance Scale, and behavior as measured by the Neuropsychiatric Inventory, were assessed at baseline and after 1, 2, and 3 years in a sample of 99 LOAD patients. These subjects were drug naive and had undergone the first clinical examination for the diagnosis of AD. RESULTS: A multiple regression analysis indicated that the presence of ApoE epsilon4 allelic variant or GSTT1 null phenotype predicted the faster age at onset of the illness (F = 5.76, df = 2, 96, p = 0.0043). Carriers of GSTP1 *C allelic variant had a faster decline in cognitive functions (repeated measures analysis of variance [ANOVA]: F = 4.00, df = 3, 285, p = 0.008) and in BADLs (repeated measures ANOVA: F = 5.27, df = 3, 285, p = 0.001). This faster decline was independent from ApoE epsilon4 allele possession. No effect of GST P1-M1-T1 polymorphisms was found on behavioral symptom severity. CONCLUSION: These data are in line with the hypotheses that oxidative damage is a prominent feature in the clinical progression and the age at onset of LOAD.
Authors: Shanker Swaminathan; Li Shen; Sungeun Kim; Mark Inlow; John D West; Kelley M Faber; Tatiana Foroud; Richard Mayeux; Andrew J Saykin Journal: Curr Alzheimer Res Date: 2012-09 Impact factor: 3.498
Authors: Omar Šerý; Tomáš Zeman; Kateřina Sheardová; Martin Vyhnálek; Hana Marková; Jan Laczó; Jan Lochman; Petr Kralik; Kamila Vrzalová; Radka Dziedzinska; Vladimir J Balcar; Jakub Hort Journal: Sci Rep Date: 2022-06-29 Impact factor: 4.996