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 develo...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.展开更多
Alzheimer’s disease (AD) is accompanied by elevated levels of homocysteine (Hcy). Homocysteine may induce elevated concentration of asymmetric dimethylarginine (ADMA). Both Hcy and ADMA are the amino acids thought to...Alzheimer’s disease (AD) is accompanied by elevated levels of homocysteine (Hcy). Homocysteine may induce elevated concentration of asymmetric dimethylarginine (ADMA). Both Hcy and ADMA are the amino acids thought to represent risk factors of vascular diseases. Studies were conducted on the plasma levels of Hcy and methionine (Met), estimated by HPLC with electrochemical detection, as well as on levels of ADMA and arginine (Arg), estimated by HPLC with fluorescent detection, in the AD patients with benign through to severe dementia estimated by MMSE scale and in a control group. The studies disclosed elevated levels of Hcy and ADMA in AD (Hcy, p < 0.001) as compared to controls, as well as in subjects older than 60 years of age (Hcy, p < 0.01). The AD patients with severe dementia have shown elevated levels of Hcy (p < 0.05) as compared to the patients with moderate dementia. The concentration of Metand Arg showed a downward trend in AD patientswith severe dementia. The highest levels of ADMA have been demonstrated in AD patients in the early stages of the disease. In parallel, in AD with varying degrees of dementia and subjects older than 60 years of age a disturbed turnover was observed of Hcy to Met and of Arg to ADMA. Similarly to Hcy, ADMA seems to be a potential risk factor of AD and important factor for progress of dementia.展开更多
文摘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.
文摘Alzheimer’s disease (AD) is accompanied by elevated levels of homocysteine (Hcy). Homocysteine may induce elevated concentration of asymmetric dimethylarginine (ADMA). Both Hcy and ADMA are the amino acids thought to represent risk factors of vascular diseases. Studies were conducted on the plasma levels of Hcy and methionine (Met), estimated by HPLC with electrochemical detection, as well as on levels of ADMA and arginine (Arg), estimated by HPLC with fluorescent detection, in the AD patients with benign through to severe dementia estimated by MMSE scale and in a control group. The studies disclosed elevated levels of Hcy and ADMA in AD (Hcy, p < 0.001) as compared to controls, as well as in subjects older than 60 years of age (Hcy, p < 0.01). The AD patients with severe dementia have shown elevated levels of Hcy (p < 0.05) as compared to the patients with moderate dementia. The concentration of Metand Arg showed a downward trend in AD patientswith severe dementia. The highest levels of ADMA have been demonstrated in AD patients in the early stages of the disease. In parallel, in AD with varying degrees of dementia and subjects older than 60 years of age a disturbed turnover was observed of Hcy to Met and of Arg to ADMA. Similarly to Hcy, ADMA seems to be a potential risk factor of AD and important factor for progress of dementia.
