Expression And Significiance Of PKR In Lymphocytes Of Alzheimer's Disease, Mild Cognitive Impairment And Parkinson's Disease Patients

Alzheimer's disease (AD) occurred in elderly and senile, is adegenerative diseases of central nervous system with cognitive impairmentand the damage of behavioral characteristics. Alzheimer's disease (AD) is themost common type of senile dementia,mainly progressive overall cognitiveimpairment.Mild cognitive impairment (MCI), is considered to be thepreclinical of AD, refers to memory impairment but not to the degree ofdementia. In China,the population is120000000whose age over60years old.The prevalence of dementia is3-8%, of which more than60%for Alzheimer'sdisease. Accoding to this proportion, in our estimation, there are400-500million AD patients in our matherland.Parkinson disease (PD), also known as paralysis agitans (shaking palsy,paralysis agitans), is a kind of degenerative diseases of the nervous system,usually occurred in elderly. PD named with the British doctor JamesParkinson who first systemic described the symptoms in1817. PD onsetsbetween the age of40-70years old,50-60year old for the peak of incidence.In our country, prevalence rate that people aged between55-65years old is1%, and advancing as while as the increase of age. Male slightly higher thanthe female.With the process of aging, the incidence rate of both Alzheimer's diseaseand Parkinson's disease is rising year by year. In particular, AD has becomethe fourth diseases result in death after tumor, cardiovascular disease,cerebrovascular disease.AD and PD were severely affects the life quality ofpatients, bring heavy economic burden to the family, government and society.At home and abroad, study of neuronal damage after animal experimentsand the autopsy are more than other ways, mainly discusses the pathogenesis of AD cell apoptosis, cell cycle dysregulation and the immanent connection ofthese mechanisms. However, early diagnosis of AD, found that MCI patientsis the base to develop therapeutic strategies and control the disease process.Recent research indicates that, in Alzheimer's disease, cell apoptosis and cellcycle regulation disorder not only limited to neurons, but also in peripheralblood lymphocytes and fibroblasts. Lymphocytes for the study of cell cyclerelated events in the pathogenesis of AD and looking for intervention targetsprovides a convenient and useful model.The collection of peripheral blood is convenient, peripheral bloodlymphocytes (peripheral blood lymphocytes, PBLs) is the lymphocytes inblood circulation. Mainly consist T cells (about70%-80%) and B cells (about20%-30%). Therefore, in-depth study can provide a convenient effectiveperipheral markers and drug intervention targets for the early diagnosis of AD.If we can obtained a simple and effective markers from peripheral blood, itmaybe important significance for early diagnosis and treatment ofAD.However, there is no such markers for clinical application so far.The double stranded RNA-dependent protein kinase (PKR), is a serine/threonine protein kinase, which is a specific protein kinase of eukaryoticinitiation factor2α (eIF-2α), double-stranded RNA can grants or inhibitis of itsactivity. Actived PKR can form a homo dimer, and autophosphorylation on aplurality of serine/threonine residues, then catalysis its substrate eIF-2αphosphorylation, thereby reducing or inhibiting protein synthesis andtranslation, play an important role in signal transduction, stress, cell growth,cell differentiation and apoptosis. PKR can also leads to tumor andinflammation by activate NF-κB, P53which is closely related to apoptosis.Almost there are PKR basal level of expression in all the cell types, withinterferon of inducers can make the increased expression of5-10times.Currently, PKR is regard as a key target of Alzheimer's disease.Therefore, the research about whether it can be a peripheral biological markerassociated with cognitive decline is feasibility and necessity.This topic make clinical patient as the object, research the level of PKR protein in peripheral blood lymphocytes of AD patients, contribute to theearly diagnosis and treatment.Objective:1Research the associated kinase PKR, P-PKR expression oflymphocytes, provide cell model for AD intervention targets.2Looking for the early diagnosis of AD in peripheral blood lymphocytesto study the apoptosis and cell cycle regulation related kinase PKR, P-PKRexpression.3At the same time, make it clear that the indicators' sensitivity andspecificity through the the research of PKR, P-PKR levels in peripheral bloodlymphocyte of normal, mild cognitive impairment patients and Parkinsondisease patients.Methods:1Selection patient according to the diagnostic criteria andexclusion criteria, collection patients of neurology outpatient department inThe Second Hospital of Hebei Medical University from September,2010toOctober,2011.Including20AD patients,20MCI patients,20PD patients,20healthy controls.Ask for patients' consent, using the Mini-Mental StateExamination (MMSE), the clinical dementia rating scale (CDR)comprehensive evaluates of the degree of cognitive impairment and record thepatients' informations.2Extracted fresh venous blood into anticoagulation tube, upside downseveral times, after centrifugal washing, extractes peripheral bloodlymphocytes with the human lymphocyte isolation liquid.3Extracted total protein from peripheral blood lymphocytes, usingWestern Blotting technology, detected the level of PKR, P-PKR were at theprotein expression level.4Statistical processing. Using the SPSS17.0statistical software packagefor processing.Results:1PKR, P-PKR levels in AD patients' peripheral bloodlymphocyte increased than that in group MCI, group PD, and increasedsignificantly normal controls.2PKR, P-PKR levels in peripheral blood lymphocytes of MCI group and PD group is nearly the same, and increased compared to the normal controlgroup, but the increase is not obvious.3PKR, P-PKR levels in peripheral blood lymphocytes were negativecorrelated with MMSE score, CDR score, but not significantly related topatients' age and duration of illness.Conclusions: It is difficult to diagnosis Alzheimer's disease earlierbecause AD often asymptomatic. Threre are PKR, P-PKR expressed inpatients' peripheral blood lymphocytes with Alzheimer's disease, mildcognitive impairment, Parkinson patients and normal human. The onlydifferent is the quantity of expression. PKR can be associated with othermarkers together as peripheral blood markers in the diagnosis of AD.