Expression And Significance Of PI3K/Akt Signaling Pathway In Peripheral Lymphocytes Of Alzheimer's Disease And Parkinson's Disease Patients

Objective: Alzheimer's disease (AD) and Parkinson's disease (PD) areneural degenerative diseases and the incidences of those diseases are increasewith age growing. AD is the most common reason of elders' dementia. Thefocal point of clinical work is how to diagnose in the early stage of AD andinterfere in its progress. However, up to now there is not safety peripheralbiomarker for diagnosis. Multiple study evidences suggested that neuronsreentering cell cycle and leading cell cycle disorder may be the pathobiologybasis of AD. Neurons death and lost are the main pathologic characteristics ofAD and cell cycle disorder may provide a new way to study the neurons deathin AD. Neurons are in the differentiation end of mitosis in normal brain. Whenneurodegenerative happened, neurons would be division and proliferation andreenter the cell cycle. Nevertheless the neurons who are forced into cell cycledon't differentiate but go to death. The disorder of cell cycle restarting can beseen in every stage of AD progression and it may be the earliest event of ADprocess. Researches suggest that cell cycle disorder and apoptosis are in earlystage of AD and are not limited in neurons but also in human peripheral cellssuch as peripheral blood lymphocytes. PI3K/Akt signaling pathway play animportant role in cell cycle regulation and apoptosis. On these ground, thisexperiment try to investigate Akt and its activated status levels of expressionin peripheral lymphocytes (PBLs) of AD and contrasted with PD patients andhealth examination elders to explore the correlations of PI3K/Akt signalingpathway and AD and PD, providing experiment evidences for convenient andsafety peripheral biomarkers and potential therapy targets of AD.Methods:40patients were involved from the Second Hospital of HebeiMedical University during the period of2010.10~2011.10. Including:(1)20 patients of probable mild and moderate AD(7males,13females), applied theclinical diagnosis criteria of the national institute of neurological andcommunicative disorders and stroke and the Alzheimer's disease and relateddisorders association (NINCDS-ADRDA) and involved patients were notfamily AD patients.(2)20PD patients (8males,12females), didn't havecognitive disorders and coincidence with PD diagnosis criteria of ChineseMedical Association (C.M.A.) announced in2006.20healthy controls of thecorresponding time period were health examination elders and there was nodifferences in constituent ratio of aging and gender and cognition functionswere normal by neuropsychological test. All subjects underwent venous bloodsampling. Peripheral lymphocytes were isolated by Ficoll-Hypaque densitygradient centrifugation. Abstracted protein by total protein abstraction kitadding protease inhibitor and protein phosphatase inhibitor. After detectedprotein concentration by BCA method, Akt and phospholated Akt (p-Akt)levels of expression in lymphocytes were detected by western blotting and thechanges of total and activated Akt levels were analyzed in three groups. Thecorrelations of Akt expression levels and diseases durations and severities ofAD and PD were detected by Pearson's correlation analysis.Results: Both total Akt and activated status levels were augmented inPBLs of AD patients in compared with controls (p＜0.05) and total Akt levelswere positively correlated with the disease duration and cognitive severity(r=0.602,p=0.014；r=-0.560,p=0.024). However, only p-Akt levels weresignificantly increased in lymphocytes of PD compared with controls (p＜0.05)and there was no correlation between Akt levels and clinical situation of PD.Conclusions: Cell cycle disorders and apoptosis are two mainpathomechanism of neurodegenerative diseases. PI3K/Akt signaling pathwayplays an important role in controlling cell cycle and apoptosis, and is widelyinvestigated in neurodegenerative diseases. However, there is few researchesof PI3K/Akt signaling pathway in peripheral lymphocytes and reports has notshow that biomarkers are directly detected without interventions inneurodegenerative diseases yet. Our research result suggests that total Akt and p-Akt expression levels are significantly increased in AD lymphocytes andAkt levels in AD lymphocytes correlate with duration and disease severity. Allthe results demonstrate that the pathological manifestations of AD are not onlylimited in neurons of central neural system but also can be detected inperipheral lymphocytes indicating that AD is a system disease. Our resultsalso suggests Akt may be a potential peripheral biomarker of early diagnosisand patients condition estimations during AD processes and provide potentialintervention target for therapy of AD.