The purpose of this study was to determine the level of 8-oxo-2'-deoxyguanosine (8-oxo2dG) and expression of three isoforms of 8-oxoguanine glycosylase 1 (OGG1), OGG1-1a, 1b, and 1c, and OGG1 protein and Ser326Cys and Arg46Gln polymorphisms of the OGG1 gene, in peripheral blood lymphocytes of patients with Alzheimer's disease (AD) and healthy controls. The study was performed in 41 AD patients and 51 healthy subjects. The level of 8-oxo2dG was determined by high performance liquid chromatography/electrochemical; expression of OGG1-1a, 1b, and 1c by real-time quantitative polymerase chain reaction; and OGG1 protein by Western blotting. The polymerase chain reaction-restriction fragment length polymorphism analysis was conducted to analyze the Ser326Cys and Arg46Gln polymorphisms. It was found that AD patients and controls have three isoforms, OGG1-1a, 1b, and 1c. The OGG1-1c isoform seems to be associated with early stage of AD, while an increase in the expression of the OGG1-1b isoform and levels of OGG1 protein appears to be similarly related to the progression of AD. All of the studied OGG1 isoforms show a decreased expression in advanced AD. The CG Ser326Cys genotype seems to have a tendency to decrease 8-oxo2dG via control of repair mechanisms. The Arg46Gln polymorphism is not associated with the pathogenesis of AD. It appears that the OGG1-1a, 1b, and 1c isoforms are involved in the pathogenesis of AD.

An elevated concentration of total homocysteine (tHcy) in plasma and cerebrospinal fluid is considered to be a risk factor for Alzheimer's disease (AD) and Parkinson's disease (PD). Homocysteine (Hcy) levels are influenced by folate concentrations and numerous genetic factors through the folate cycle, however, their role in the pathogenesis of PD remains controversial. Hcy exerts a neurotoxic action and may participate in the mechanisms of neurodegeneration, such as excitotoxicity, oxidative stress, calcium accumulation, and apoptosis. Elevated Hcy levels can lead to prooxidative activity, most probably through direct interaction with N-methyl-D-aspartate (NMDA) receptors and sensitization of dopaminergic neurons to age-related dysfunction and death. Several studies have shown that higher concentration of Hcy in PD is related to long-term administration of levodopa (L-dopa). An elevation of plasma tHcy levels can also reflect deficiencies of cofactors in remethylation of Hcy to methionine (Met) (folates and vitamin B12) and in its transsulfuration to cysteine (Cys) (vitamin B6). It is believed that the increase in the concentration of Hcy in PD can affect genetic polymorphisms of the folate metabolic pathway genes, such as MTHFR (C677T, A1298C and G1793A), MTR (A2756G), and MTHFD1 (G1958A), whose frequencies tend to increase in PD patients, as well as the reduced concentration of B vitamins. In PD, increased levels of Hcy may lead to dementia, depression and progression of the disease.

Summary:Purpose: To identify mutations of the neuronal nicotinic acetylcholine receptor α4 subunit gene (CHRNA4) responsible for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) in a group of white patients.Methods: A group of 47 patients from 21 unrelated families with ADNFLE were screened for mutations in CHRNA4. Clinical features and EEG findings in the patients were consistent with those reported in the literature for other affected families. The entire gene was amplified from genomic DNA by polymerase chain reaction (PCR) followed by multitemperature singlestrand conformation polymorphism analysis (MSSCP) and sequencing.Results: A c.851C>T transition in exon 5 of CHRNA4 was identified in three affected individuals from two generations of the same family, but not in the remaining patients or in 100 healthy volunteers. This mutation caused an S284L substitution in the transmembrane domain M2 segment of the α4 subunit of the neuronal nicotinic acetylcholine receptor. The same mutation had previously been detected in a single Japanese family with ADNFLE, and in an Australian woman with a sporadic form of NFLE.Conclusions: This is the first report of an occurrence of c.851C>T transition in a white family with ADNFLE.

It is possible, that polymorphisms of genes related to Hcy-to-Met metabolism, in epileptics treated with AEDs may have an effect on the regulation of levels of risk factors of vascular diseases, Hcy and ADMA.