Glutathione s-transferase p1 and t1 gene polymorphisms predict longitudinal course and age at onset of alzheimer disease

Gianfranco Spalletta, Sergio Bernardini, Lorenza Bellincampi, Giorgio Federici, Alberto Trequattrini, Fabrizio Ciappi, Pietro Bria, Carlo Caltagirone, Paola Bossù

Research output: Contribution to journalArticlepeer-review

Abstract

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) ε4 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 ε4 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 ε4 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.

Original languageEnglish
Pages (from-to)879-887
Number of pages9
JournalAmerican Journal of Geriatric Psychiatry
Volume15
Issue number10
DOIs
Publication statusPublished - Oct 2007

Keywords

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

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology

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