Expression And Significance Of Telomere Length And Telomere-associated Protein In Peripheral Blood Mononuclear Cells In Patients With AD

Background and ObjectiveAs the most common senile disease in human beings,Alzheimer's disease(AD)is a kind of primary degenerative encephalopathy that occurs in the senile period and the early senile period.According to the epidemiological survey results,the prevalence of AD in the elderly aged 65 years or older in China is 3% ~ 8%,and the prevalence increases year by year with the increase of age.Therefore,it is necessary to further study its pathogenesis and diagnostic methods.Pathologically,though,loss of synapses and neurons,extracellular senile plaques,and intracellular neurofibrillary tangles(NFT)were observed in the brains of AD patients.These features are associated with changes in A?(amyloid beta)40,A?42,total Tau,and phosphorylated tau(p-Tau),which are clear cerebrospinal fluid biomarkers of severe AD status.However,there is a lack of practical,simple and feasible biomarkers that can effectively diagnose AD to guide treatment strategies.Telomeres are closely related to senescent diseases and are receiving increasing attention in AD.Telomeres are important structures of chromosomes and play an important role in maintaining the stability of chromosomes.Telomere length,telomerase and telomere associated proteins constitute the telomere system,which together maintain telomere stability.There are different degrees of telomere loss or telomere instability in cell senescence.Studies have found that telomere shortening is a linear factor of cognitive impairment,and the length of leukocyte telomere may be related to the cognitive ability of healthy women,suggesting that it may be a biomarker of cognitive aging in women before the onset of AD.In this study,telomere length and telomere related protein activity of peripheral blood mononuclear cells were detected by molecular biology methods to explore the correlation between telomere length change,telomere protein activity change and AD in peripheral blood.Materials and MethodsExtraction of 42 patients with Alzheimer's disease(AD)(light,medium,heavy,respectively in patients with AD have 10 people,17 people,15 people)genomic DNA of peripheral blood mononuclear cells using RT-PCR(Reverse Transcription-Polymerase Chain Reaction)method for detection of genomic DNA of telomere length and telomerase related protein TRF1,TRF2,POT1 mRNA expression levels,detection of AD patients and normal healthy human telomere length changes and related protein expression levels,To explore the effect of Alzheimer's disease on the telomere length and telomere protein of human peripheral blood mononuclear cells.To explore the correlation between different degrees of severity of Alzheimer's disease and the changes of telomere length and the expression level of related proteins in peripheral blood mononuclear cells.To explore the correlation between telomere length,TRF1,TRF2 and POT1 of peripheral blood mononuclear cells in patients with Alzheimer's disease.ResultsThe telomere length of peripheral blood mononuclear cells in AD patients was smaller than that of the healthy control group(NC)(P<0.05).mRNA expression levels of telomere associated proteins TRF1,TRF2 and POT1 in AD patients were higher than those in the NC group(P<0.05).The telomere length of mild,moderate and severe AD patients was smaller than that of NC group(P<0.05),and the telomere length of severe dementia patients was lower.mRNA expression levels of telomere associated proteins TRF1,TRF2 and POT1 in the three groups of AD patients with severe AD were all higher than those in the NC group(P<0.05),and the expression levels of high-end granule related proteins increased with the increase of AD severity.The area under the ROC curve of telomere length,TRF1,TRF2 and POT1 for diagnosing AD was 0.716,0.726,0.75 and 0.717,respectively.Telomere length was correlated with the expression levels of TRF1 and TRF2 mRNA,and the correlation coefficients were R=-0.562,R=-0.434 and P < 0.05,respectively.There was a correlation between POT1 and TRF1 m RNA expression level,R=0.388,P < 0.05.ConclusionsThe telomere length of peripheral blood mononuclear cells in Alzheimer's disease patients is significantly shorter than that in normal people,and the telomere length is significantly shortened as the severity of AD patients increased.Telomere associated proteins TRF1,TRF2 and POT1 may be involved in the process of telomere length change and participate in the occurrence and development of Alzheimer's disease.Telomere length is negatively correlated with telomere associated proteins TRF1 and TRF2,while POT1 is positively correlated with TRF1,suggesting that TRF1 and TRF2 may be involved in the process of telomere shortening.POT1 may indirectly participate in telomere loss by affecting TRF1,and short telomeres are closely related to the occurrence and development of Alzheimer's disease.Detection of peripheral blood telomere length,TRF1,TRF2,and POT1 may be important indicators for assessing the risk and prognosis of Alzheimer's disease.