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Am J Geriatr Psychiatry 15:879-887, October 2007
© 2007 American Association for Geriatric Psychiatry
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Article

Glutathione S-Transferase P1 and T1 Gene Polymorphisms Predict Longitudinal Course and Age at Onset of Alzheimer Disease

Gianfranco Spalletta, M.D., Sergio Bernardini, Ph.D., Lorenza Bellincampi, Ph.D., Giorgio Federici, M.D., Alberto Trequattrini, M.D., Fabrizio Ciappi, M.D., Pietro Bria, M.D., Carlo Caltagirone, M.D., and Paola Bossù, Ph.D.

From the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Rome (GS, GF, CC, PB); the Departments of Neuroscience (GS, CC), Internal Medicine (SB, LB, GF), and Laboratory Medicine (SB, LB, GF), University Tor Vergata, Rome; Azienda Sanitaria Locale Città di Castello, Perugia, (AT, FC); and the Catholic University of the Sacred Heart, Institute of Psychiatry, Rome (PB), Italy.

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) {varepsilon}4 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 {varepsilon}4 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 {varepsilon}4 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.

Key Words: Alzheimer disease • late onset • glutathione S-transferase • cognition • activities of daily living • outcome • oxidative stress






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