Study On Dependablity Between The Activity Of Glycogen Synthase Kinase-3β And Mild Cognitive Impairment

Mild cognitive impairment (MCI) is a cognitive impairment state between normal aging and dementia, it manifests that memory loss or other non-memory cognitive regions damage dose not commensurate with age, but dose not meet dementia. A considerable part of MCI patients will eventually progress to dementia. Therefore, MCI is a high risk status of developing to dementia. It has positive significance to prevent the occurrence of dementia by early detection and intervention in MCI.MCI epidemiological studies is limited since the lack of uniformity in diagnostic criteria, and differences in the survey methods and surveyed population. Now it is necessary to do a large sample and standardized epidemiological survey adopting uniform definitions, concepts which diagnostic criteria easy to execute, and representative natural populations. Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/ threonine kinase, commonly found in eukaryotic cell biology.It including two subtypes in mammals,namely, GSK-3αand GSK-3β, molecular weight of 51kD and 47kD. Phosphorylation of GSK-3αin the 21th serine and GSK-3βin the ninth serine could inhibit the activity of GSK-3. Many human diseases such as diabetes, cancer, neurodegenerative diseases, affective disorders and inflammation diseases relate to abnormal regulation of GSK-3βactivity. Glycogen synthase kinase-3βis abundant in brain tissue particularly. Glycogen synthase kinase-3β(GSK-3β) in MCI and AD disease process not only involves inβ-amyloid (Aβ) production, but also relates with hyperphosphorylation of tau protein closely. Aβand tau protein is directly involved in senile plaques (SP) and neurofibrillary tangles (NFT) formation. Therefore, it has important basic and clinical value to research the relevance of GSK-3βand MCI. The subject did a epidemiological survey about cognitive function for over 65 yearsolders lived in part of the community in Changchun city, mastered the overall prevalence rate of mild cognitive impairment (MCI) and dementia of urban community aged, analyzed the population distribution and related risk factors to explore the epidemiological characteristics of MCI. At the same time, selected part of the population randomly from the screened MCI patients and normal subjects, and then measured the expression and activity of glycogen synthase kinase-3β(GSK-3β) in their peripheral blood lymphocytes in order to clear the correlation between GSK-3βwith MCI.Experimental method:Adopting the cluster sampling method, selected the 65 years of age or older from 10 communities of the first automobile works community, Nanguan area and Lvyuan district in Changchun City as the survey. The graduate students from department of Neurology, First Hospital of Jilin University get into the community to investigate after training and testing the consistency. The total number of 65 years and older of 10 communities was about 3000, and the actual number of persons investigated was 1904. Adopting stratified multiple stage sampling method, pre-divided the overall investigation into normal group, MCI group. Then pre-selected 30 from each group. On the day after epidemiological investigation, took their fasting venous blood 3ml, and extracted lymphocytes and cryopreservated the same day. Detected the expression and activity of glycogen synthase kinase-3βwithin lymphocytes adopting Immunohistochemical method, and determined the differences of results by image analysis.Experimental results:In the surveyed 1904 older people from 10 communities, men have 831, women have 1073, including 304 MCI patients and 41 dementia patients. The overall prevalence of MCI is 15.97%, the dementia is 2.15%. In addition, the population distribution and risk factor analysis showed that: there is significant correlation between mild cognitive impairment and age, education, occupation, marital status, as well as sleep, exercise, hypertension, diabetes, stroke, hyperlipidemia, history of epilepsy. The elderly, low education level, widowed and those with hypertension, diabetes, stroke, and hyperlipidemia are risk factors for MCI. Through detected the expression of GSK-3βand its phosphorylation level (pGSK-3βser9), we found that the expression of GSK-3βhave no significant difference between the normal group and MCI group, while the pGSK-3βser9 was significantly lower, there were significant differences. These results reflect that the activity of GSK-3βin MCI group is higher than normal group, indicate that the GSK-3βactivity in peripheral blood lymphocytes is positively correlated with the occurrence of MCI.Experimental conclusion:1. In Changchun city, the overall prevalence of mild cognitive impairment of the community 65 years and older is 15.97%, and dementia is 2.15%.2. there is significant correlation between mild cognitive impairment and age, education, occupation, marital status, as well as sleep, exercise, hypertension, diabetes, stroke, hyperlipidemia, history of epilepsy. The elderly, low education level, widowed and those with hypertension, diabetes, stroke, and hyperlipidemia are risk factors for MCI.3. The expression of GSK-3βhave no correlation with the MCI, while the activity of GSK-3βhas positive correlation with the incidence of MCI.