TITLE:
Mutations of TP53 Gene and Oxidative Stress in Alzheimer’s Disease Patients
AUTHORS:
Jolanta Dorszewska, Agata Różycka, Anna Oczkowska, Jolanta Florczak-Wyspiańska, Michał Prendecki, Mateusz Dezor, Izabela Postrach, Paweł P. Jagodzinski, Wojciech Kozubski
KEYWORDS:
TP53; 8-oxo2dG; p53; OGG1; AD
JOURNAL NAME:
Advances in Alzheimer's Disease,
Vol.3 No.1,
March
12,
2014
ABSTRACT: Alzheimer’s disease (AD) leads to the generation of β-amyloid (Aβ), which may damage DNA and thus lead to apoptosis induction by the p53 pathway. Dysfunction of the p53 protein may then be connected with the development of AD. Studies were conducted on 28 AD patients and 30 non-AD controls. Analysis of TP53 mutations in exon 7 was performed on DNA isolated from whole blood and biochemical parameters in the peripheral lymphocytes of these individuals. Our study showed a silent mutation TP53 C708T (21%) [p TP53 C748A (4%) only in the AD patients. Moreover, in AD patients with the TP53 C748A mutation, the level of 8-oxo-2’- deoxyguanosine (8-oxo2dG) was more than 5 times higher than the average level in this study group. In AD patients with the wild-type TP53 gene, the level of 8-oxo2dG was correlated with the level of protein p53 (R = +0.7388, p TP53 (p TP53 (C748A, C708T) may be associated with pathogenesis of AD.