The Clinical Studies Of Mitochondrial Dynamic Related Genes In Alzheimer’s Disease

Background and purpose:Alzheimer’s disease (AD) is a central nervous system degenerative disease which is characterized by progressive cognitive dysfunction and behavioral impairment. It’s the most frequent cause of elderly dementia which is manifestation with progressive memory disorders, personality and behavior change. The incidence of AD rise year by year, the global economic burden of dementia is also increasing year by year. So far, however, the AD is still lack of effective treatment methods. Therefore, further defined the etiology and pathogenesis of AD, and to explore new methods of prevention and treatment of AD is particularly urgent.Mitochondria is important in cell physiological functions, including the synthesis of ATP, calcium ions in the steady state, produce reactive oxygen species (reactive oxygen species, ROS) and the regulation of apoptosis signal, etc., so the mitochondria has the vital role in cell survival and death especially for neurons and other cells. A growing number of studies show that mitochondrial dysfunction involved in the pathological process of neuron degeneration through mitochondrial dynamics (mitochondrial dynamics) and mitochondrial autophagy (mitophagy) and other mechanisms. Mitochondrial dynamics means mitochondria in cell fission and fusion, mitochondrial division is mainly composed of sample dynein protein (dynamin-like protein, Drp1), and raise through the mitochondrial outer membrane of mitochondria protein 1 (fission 1, Fisl) and mitochondrial division factor (mitochondrial fission factor, Mff). Mitochondria fusion is mainly composed of mitochondrial protein 1 (mitofusin 1, Mfn1) and mitochondria fusion protein 2 (mitofusin 2, Mfn2) and Opal which is located in the mitochondrial membrane. A study shows expression of mitochondria dynamics related molecular in transfection APP cells are abnomol. A study shows multiple genes in cerebrospinal fluid, brain tissue and blood in patients with AD mRNA level change which provide the basis for pathogenesis and diagnosis of AD, but whether mRNA levels of the mitochondrial dynamics related molecular in the blood have change remains to be studied.Found in recent years, A variety of AD biological markers, such as A beta 1-42 of cerebrospinal fluid, the total phosphorylated tau tau, cerebrospinal fluid, some biological molecules can play A role in the diagnosis of AD, such as platelet APP ratio, F2-isoprostanes in cerebrospinal fluid and plasma heme oxygenase inhibitory factor and so on, but due to reasons such as expression is not stable, still cannot as AD diagnosis of stable biological marker.Therefore, this study from clinical AD patients and control group in blood collection, determination of mitochondrial dynamics related genes mRNA level of change, further study the pathogenesis of AD, and provide feasible biological markers for early diagnosis of AD.Methods:1. Collect the blood specimens of control group and patients with AD;2. Rt-PCR detection the mRNA level of mitochondrial dynamics related molecules, OPA1、Drp-1.Results:1. Collecting blood samples, a total of 27 patients with AD, clinical neurology outpatient and inpatient in the second hospital of Shandong university. All criteria for the patients according to the 2011 revised edition of the 1984 national institute of neuropathy and the language barrier, and stroke NINCDS-alzheimer’s disease and related disorders learn ADRD diagnostic criteria.11 cases of men and women in 16 cases, with an average age of 73.33 years. All patients have simple mental health checks inventory MMSE and clinical dementia rating scale CDR detection, and simple classify the dementia severity based on the MMSE score, mild 0 in 27 patients with clinical cases,10 cases of moderate and severe 17 cases.2. The control group:a total of 27 cases, all are elderly people doing physical examination in the healthy physical examination center of the second hospital of shandong university.11 cases of men and women in 16 cases, with an average age of 69.07 years. Gender match with AD cases exactly, age can’t completely match case group, but no statistical difference between two groups by statistical analysis. Control group standard:1)No delirium or other mental system disease; 2) MMSE 27 points or higher; 3)Without a recent trauma, surgery, hemorrhage of intracranial infection, viscera disease history; 4)Without coronary heart disease, severe hypertension, high cholesterol, diabetes, epilepsy, poisoning, liver and kidney dysfunction, malignant tumor history and so on; 5)The detailed explanation to the research and all informed consent;3.RT-PCR results:gather all the research object’s empty stomach EDTA anticoagulant blood on the morning for 3 to 5 ml, by RT-PCR detection, RQ= 2-△ △ CT method and IBM SPSS 22.0 statistical analysis. Among this, comparison between the case group and control group by independent samples t test, various factors such as age, gender differences in the group with single factor analysis of variance method, p< 0.05 statistically significant.1) Two groups in age, sex, no statistical difference.2) Compared with the control group, Drp1、Opa1 gene mRNA level in peripheral blood are higher in case group, Drpl gene rising trend is more obvious.3) In the case group Drpl gene mRNA level has gender differences, women about men 2 times; Cases, respectively, compared with the control group in men and women, the gene level are higher in the group, women rise trend is more obvious.4) Opal expression level in the case group and the control group have gender differences, women more than men; Respectively compared with the control group in men and women, the level of the gene rise in case group.5) Cases in different age stages Drp1, Opal mRNA level no obvious difference.6) Cases in moderate and severe patients with no difference between the two gene expression levels.Conclusion:1. The mitochondrial fission protein Drp1 mRNA level in the blood of AD patients increased significantly, the fusion protein OPA1mRNA level also increased,.2. Drpl higher genetic level in the Small sample of alzheimer’s patients blood specimens, which can provide new direction and basis for biological markers in early diagnosis of AD research.