| Research background and purposeAlzheimer’s disease(AD)is the most common type of dementia.Typical cases initially show a decline in recent memory.With the progress of the disease,patient’s cognitive function is completely lost and he can not take care of himself.At present,there are about 50 million dementia patients in the world.AD accounts for about 2/3 of the total number of dementia,which has become the fifth leading cause of death in China.With the aging of the population,the incidence of AD is becoming more and more serious,which is a global medical problem to be solved.At present,there is no radical treatment for this disease,but if the intervention treatment is carried out as soon as possible,the disease progress can be delayed to a certain extent and the quality of life of patients can be improved.Scientists have been trying to develop new drugs for AD,but most of them failed.The important reason is that the research window is too backward.In fact,pathological changes begin to appear in the brain 15 to 20 years before the symptoms appear.Therefore,early diagnosis of AD is particularly important.The importance of biomarkers in the diagnosis of AD has become a consensus,especially for the diagnosis of ultra early AD without clinical symptoms.At present,cerebrospinal fluid(CSF)amyloid-beta 42(Aβ42)and tau protein are recognized diagnostic markers.However,due to the invasive nature of lumbar puncture,it is difficult to obtain CSF for AD patients,which limits its wide application.Amyloid PET-CT can show the deposition of Aβ in the brain in vivo,which can be used as a promising imaging marker.However,due to the high cost of PET-CT scanning and the need for special tracer,it is used in scientific research and is difficult to carry out in clinical practice.Therefore,there is still a lack of small trauma,cheap and easily accepted markers for AD.The etiology of sporadic AD is complex,and the pathogenesis is still unclear.Studies have shown that exosomes and lncRNAs are involved in the pathophysiological process of AD.Exosomes are a group of small extracellular vesicles,which participate in neuronal regeneration,development and synaptic formation.They contain proteins closely related to the pathogenesis of AD,such as APP,β-secretase,γ-secretase and Aβ.and can transfer toxic proteins between nerve cells.Exosomes can pass through blood brain barrier(BBB)freely and can be detected in cerebrospinal fluid,blood,saliva and other body fluids.Exosomes can be used as biomarkers for various nervous system diseases,such as Parkinson’s disease,prion disease and progressive stroke.Long chain non encoding RNAs(lncRNAs)mainly influences gene expression and disease through the epigenetic regulation,transcription and post transcriptional regulation of genes.LncRNA is highly expressed in the brain,which can participate in the pathogenesis of AD by regulating A(3 production,oxidative stress,synaptic damage,mitochondrial dysfunction and so on.It was found that there were many abnormal lncRNAs expression in AD patients compared with the control group.Structural magnetic resonance imaging(sMRI)is the most basic means of magnetic resonance examination,which is widely used in clinical practice.Combined with the new computer image analysis technology,the imaging is closer to the brain anatomy,which can accurately show the location and degree of brain atrophy and the structure of various brain regions,and can exclude cognitive dysfunction caused by other brain diseases.It is the most commonly used imaging means in the diagnosis and differential diagnosis of dementia.To sum up,exosomes and lncRNAs participate in the pathophysiological process of AD,and can be detected in peripheral blood.Structural MRI can clearly reflect the degree of brain atrophy and can dynamically observe the progress of disease,and most dementia patients can cooperate to complete.Therefore,exosomes,lncRNA and sMRI imaging can be used as an ideal way to exploring AD markers.In this study,we selected several lncRNAs that were up-regulated in the brain of AD patients to verify their expression in the peripheral blood exosomes.At the same time,automatic software was used to analyze the data of medial temporal lobe subregion of subjects,in order to find clinical practical,maneuverable diagnostic markers for AD.Research objectA total of 134 chinese Han participants(72 patients with ad and 62 controls)were recruited from the Second Hospital of Shandong University between May 2014 and July 2019.They met the most likely diagnostic criteria of AD by the National Institute of aging and the Alzheimer’s disease association(NIA-AA)in 2011,excluding other diseases that may lead to cognitive dysfunction.The controls matched with AD group in age,gender and education level.All the subjects underwent head MRI and/or CT scan and neuropsychological scale test,and the general clinical information such as blood pressure,fasting blood glucose,blood lipid,hemoglobin,smoking and drinking were collected.No cerebrospinal fluid(CSF)samples were tested.This study was approved by the ethics committee of the Second Hospital of Shandong University.All subjects signed informed consent forms by themselves or their clients.Statistical methodSPSS24.0 and graphpad prism 5.0 were used for statistical analysis and chart making.Firstly,whether the continuous data conforms to the normal distribution is tested.The data conforming to the normal distribution is expressed as the mean ±standard deviation,the data of the partial distribution is represented by the median(upper quartile and lower quartile),and the classified variable data is expressed as frequency and percentage.Spearman rank correlation analysis or Pearson correlation analysis were used to analyze the correlation between two continuous variables.Student’s t-test or Mann Whitney U test was used to compare the data between the two groups.Chi square test was used to compare the categorical variables.One way ANOVA or Kruskal Wallis rank sum test was used to compare the data between groups.Receiver operating characteristic(ROC)was used to analyze the area under the curve(AUC)to evaluate the sensitivity,specificity,accuracy,Youden index and cut-off value of target RNAs.P<0.05 means statistical difference.Research Method1.Part I The study of plasmal exosomes lncRNAs as biomarkers for ADFive milliliters whole blood samples were collected from all participants in EDTA tubes and the exosomes were extracted immediately for the following studies:(1)in order to verify that the substance we extracted was exosomes,the marker proteins of exosomes were detected by Western blot,the morphology and size of exosomes were observed by electron microscopy(TEM),and the particle size and concentration of the extracted exosomes were measured by nano particle tracking analysis(NTA).(2)Reverse transcription-quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression of exosome RNA(including lncRNA BACE1-AS,51A,BC200,17A and BACE1 mRNA)in peripheral blood exosomes,and to find the differentially expressed RNA in AD and control subjects.(3)Spearman correlation analysis was performed between the differentially expressed plasma exosome lncRNAs and clinical data(such as age,onset time,MMSE score,blood lipid,etc.),and the degree of dementia was classified according to CDR score,and lncRNAs was compared among subgroups.(4)The AUC,sensitivity,specificity,accuracy,Yoden index and the cut-off value were calculated to explore the plasma exosome markers of AD.2.Part Ⅱ The study of medial temporal lobe subregion with sMRI as a biomarker of ADThe subjects with good compliance were scanned with 3D-BRAVO sequence of 3.0T MRI,and T1 axial data were collected for the following studies:(1)FreeSurfer software was used for analysing the cortical volume,mean thickness,surface area and mean curvature of the four main subregions of medial temporal lobe(including entorhinal cortex,hippocampus,parahippocampal gyrus,amygdala).They were analyzed to find out the MRI indexes of medial temporal lobe which were different from AD and control.(2)According to the score of CDR,the degree of dementia was divided,and MRI data were compared among AD subgroups.(3)Neuropsychiatric score(NPI)was used to evaluate the mental symptoms of dementia patients.AD patients were divided into two subgroups according to the presence or absence of psychiatric symptoms.(4)ROC curve analysis and diagnostic efficiency evaluation were performed on the differentially expressed sMRI indexes.AUC,sensitivity,specificity,accuracy,Youden index and cut-off value were calculated to screen image markers of AD.3.Part Ⅲ Correlation between exosomal lncRNAs and sMRI parameters of medial temporal lobeSpearman correlation analysis was performed between lncRNAs differentially expressed in AD and control subjects and MRI parameters of medial temporal lobe subregion to explore the clinical evidence and possible mechanism of lncRNAs in peripheral blood involved in AD brain atrophy.4.Part IV The diagnostic value of BACE1-AS and 17A combined with sMRI parameters of medial temporal lobe for ADThe following studies were carried out:(1)The expression of lncRNAs in AD and control group was analyzed by serial and parallel tests respectively.(2)Logistic regression model was established for the above differential expression of exosomes and imaging indexes to screen the more effective markers for combined diagnosis of AD.ResultsPart 1 The study of plasmal exosomes lncRNAs as biomarkers for AD1.1 Identification of plasmal exosomesWestern blot showed that exosomes marker proteins,Alix and CD63,could be detected in the exosomes we extracted.The morphology of exosomes was observed by electron microscopy,and it was found that the exosomes were spherical vesicles with a diameter of 30-150 nm.NTA analysis showed that the diameter of the exosomes was 16.5-478.3 nm,and 99.7%of the particles were about 98.9 nm.It can be seen that the yellow and white precipitates we extracted accord with the characteristics of exosomes.1.2 Expression of exosome RNA in plasmaRT-qPCR was used to detect the relative expression of BACE1-AS,51A.BC200.17A and BACE1 mRNA in AD and control group.The results of Mann Whitney U test showed that the expression levels of BACE 1-AS and 17A in plasma exosomes of AD patients were significantly higher than those of control group,and the other RNAs had no significant difference between the two groups.1.3 Correlation analysis of plasma exosomal BACE1-AS and 17A with clinical dataThe levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and hemoglobin(HB)in male patients with AD were lower than those in normal controls.There was no significant correlation between the expression of hcel-17a and hdas-17b and plasma levels of hcel and bac-17as.In order to explore whether the expression levels of BACE1-AS and 17A vary with age,and whether they are related to the onset time and severity of AD,the correlation between the two lncRNAs and the age,onset time and MMSE score of was analyzed.The results showed that BACE1-AS and 17A had no significant correlation with the above indexes.According to the CDR score.AD patients were divided into three subgroups:mild,moderate and severe AD.Kruskal Wallis test was used to compare the expression levels of plasma exosomal BACE1-AS and 17A between the three subgroups,and then the two subgroups were compared.The results showed that the expression of bacel-as in mild,moderate and severe AD patients was higher than that in normal controls,but there was no significant difference among the subgroups(P>0.05).The expression level of 17a in AD patients with various dementia degrees was higher than that of normal controls,but there was no significant difference among the subgroups(P>0.05).These two lncRNAs were stably expressed in AD patients with different degrees of dementia.1.4 ROC curve analysis and diagnostic efficiency evaluation of BACE1-AS and 17A were performedThe AUC of BAEC1-AS was 0.761(95%CI,0.675-0.848;P<0.001).The sensitivity,specificity and accuracy were 87.5%.61.3%,75.37%respectively and the cutoff vaule was 0.623.The AUC of 17A was 0.633(95%CI.0.5324-0.7335;P=0.012).The sensitivity,specificity and accuracy of 17A were 83.05%.45.90%,64.17%respectively and the cutoff vaule was 0.595.Conclusion:Plasma exosomal lncRNA BACE1-AS and 17A can distinguish AD patients from controls,and these two lncRNAs are stably expressed in AD patients with different degrees of dementia,which can be used as potential peripheral blood markers for the diagnosis of AD.The diagnostic test showed that BACE1-AS had better diagnostic efficiency than 17A.2.Part Ⅱ The study of medial temporal lobe subregion with sMRI as a biomarker of ADDue to the strict requirements of 3D-BRAVO MRI sequence scanning and automatic data analysis software on scanning parameters,only 22 cases of AD patients and 26 controls completed the required scanning,and the two groups matched in age,gender and education years.2.1 Comparison of structural MRI dataThe cortical volume,mean thickness,surface area and mean curvature of the four main medial temporal lobes(including entorhinal cortex,hippocampus,parahippocampal gyrus and amygdala)were analyzed between the two groups.The results showed that:2.1.1 HippocampusThe left hippocampal volume of AD patients was 3666.01 ± 1188.36 mm3,and that of controls was 4085 ± 775.80 mm3;the volume of right hippocampus of AD patients was 3926.13 ± 871.56 mm3,and that of controls was 4238.11 ± 756.22 mm3.Student’s t-test was used to compare the data between the two groups,and there was no significant difference between the two groups(P>0.05).2.1.2 Entorhinal cortexThe right entorhinal cortex volume of AD patients was 1114.68 ± 588.63 mm3,and that of control group was 1484.50 ± 365.55mm3.Student’s t-test showed that there was significant difference between the two groups,AD was significantly lower than that of the control group(P<0.05).The average thickness of right entorhinal cortex was 2.69 ± 0.44mm in AD patients and 2.97 ± 0.38mm in control group.Statistical analysis showed that the average thickness of right entorhinal cortex in AD patients was significantly lower than that in control group(P<0.05).There was no significant difference between the two groups.2.1.3 Parahippocampal gyrusStudent’s t-test was used to compare the data between the two groups.It was found that there was no significant difference in the indexes of bilateral parahippocampal gyrus between the two groups(P>0.05).2.1.4 AmygdalaThe left amygdala volume of AD patients was 1170.75 ± 402.63mm3,and that of control group was 1559.65±289.02mm3.Student’s t-test test showed that there was significant difference between the two groups,and ad was significantly reduced compared with the control group(P<0.01).The right amygdala volume of AD patients was 1342.01 ± 307.68mm3,and that of control group was 1629.97 ±250.24mm3.Student’s t-test showed that there was significant difference between the two groups,and ad was significantly reduced compared with the control group.2.2 ROC curve analysis and diagnostic efficiency evaluationAs mentioned above,the four indexes of medial temporal lobe(including right entorhinal cortex volume,right entorhinal cortex thickness,bilateral amygdala volume)in AD patients were significantly lower than those in the control group.In order to evaluate their diagnostic value,ROC curve analysis was performed.2.2.1 Right entorhinal cortex volumeThe AUC was 0.761(95%CI:0.527-0.850,P<0.05).The sensitivity,specificity,accuracy,Youden index and cutoff value were 59.1%,84.6%,72.92%,0.437 and 1142.5 respectively.2.2.2 Mean thickness of right entorhinal cortexThe AUC was 0.689(95%CI:0.536-0.843,P<0.05).The sensitivity,specificity,accuracy,Youden index and cutoff value of AD were 80.8%,59.1%,68.75%,0.399 and 2.705 respectively.2.2.3 Left amygdala volumeThe AUC was 0.761(95%CI:0.623-0.898,P<0.01).The sensitivity,specificity,accuracy,Youden index and cutoff value of AD were 80.8%,63.6%,72.91%,0.444 and 1358 respectively.2.2.4 Right amygdala volumeThe AUC was 0.771(95%CI:0.635-0.907,P<0.01).The sensitivity,specificity,accuracy,Youden index and cutoff value of AD were 88.5%,63.6%,77.08%,0.521 and 1472 respectively.2.3 MRI data and clinical data of medial temporal lobe subregion in AD patients2.3.1 Correlation between MRI parameters of medial temporal lobe subregion and dementia severityAccording to the requirements of MRI analysis,22 AD patients were graded by CDR score:mild 4 cases,moderate 10 cases,severe 8 cases.2.3.1.1 One way ANOVA was used to compare the data of three subgroups.It was found that there were significant differences in the volume and thickness of the right entorhinal cortex among the three groups.There were significant differences in the thickness of the right entorhinal cortex between mild and moderate AD(P=0.019),and the right entorhinal cortex volume was significantly different between mild and severe AD(P=0.036).2.3.1.2 One way ANOVA was used to compare the data among the three AD subgroups.It was found that there was no significant difference in bilateral hippocampal volume among the three groups,but the hippocampal volume of AD patients with different degrees of dementia was smaller than that of the control group.2.3.1.3 There was no significant difference in other MRI indexes among the three subgroups(P>0.05).2.3.2 MRI indexes and neuropsychiatric symptom score of medial temporal lobe subregionNeuropsychiatric score(NPI)can evaluate the mental symptoms of dementia patients and the pain degree of caregivers.According to NPI score of 22 AD patients,13 patients had different degrees of mental symptoms.2.3.2.1 All AD patients were divided into two groups according to whether they had mental symptoms.Student’s t-test was used for statistical analysis.It was found that the volume of bilateral amygdala and left hippocampus were significantly different between the two groups,and the atrophy of patients with mental symptoms was more serious(P=0.0002;P=0.042;P=0.009).2.3.2.2 The total score of NPI and the total score of pain of caregivers were calculated in AD patients with mental symptoms,and the correlation between NPI score and bilateral amygdala volume and left hippocampal volume was analyzed.Pearson correlation analysis showed that the total score of NPI and the total score of caregivers’ pain had no significant correlation with bilateral amygdala volume and left hippocampal volume(P>0.05).2.3.3 Comparison of bilateral medial temporal lobe dataStudent’s t-test was used to compare the indexes of bilateral amygdala,bilateral hippocampus,bilateral entorhinal cortex and bilateral parahippocampal gyrus.There was no significant difference between left and right sides(P>0.05).2.3.4 Comparison of different gender in medial temporal lobe subregionStudent’s t-test was used to compare 20 MRI indexes of medial temporal lobe in different genders.No significant difference was found between male AD patients(n=11)and female patients(n=11)(P>0.05).2.3.5 Correlation between medial temporal lobe subregion and MMSE scorePearson correlation analysis showed that there was no significant correlation between 20 MRI indexes of medial temporal lobe and MMSE score of AD patients(P>0.05).2.3.6 Correlation between medial temporal lobe subregion and onset timePearson correlation analysis showed that 20 MRI indexes of medial temporal lobe had no significant correlation with the onset time of AD(P>0.05).Conclusion:This study analyzed 20 indexes in 4 subregions of medial temporal lobe by using MRI scanning and automatic software.It was found that the right entorhinal cortex volume,right entorhinal cortex thickness and bilateral amygdala volume in AD patients were significantly smaller than those in the control group.The diagnostic test showed that the above four MRI indexes had good diagnostic value and could be used as potential imaging markers for the diagnosis of AD.CDR dementia subgroup analysis showed that the right entorhinal cortex thickness was significantly different between mild and moderate AD,and the right entorhinal cortex volume was significantly different between mild and severe AD.NPI score subgroup analysis showed that the volume of bilateral amygdala and left hippocampus were significantly different between the two groups,and the atrophy of patients with mental symptoms was more serious.Part 3 Correlation between exosomal lncRNAs and sMRI parameters of medial temporal lobe3.1 BACE1-AS and sMRI indexesSpearman correlation analysis was performed on 20 parameters of sMRI in the medial temporal lobe subregion and the corresponding expression level of BACE1-AS in plasma exosomes.It was found that there was a correlation between the right amygdala volume and the expression level of BACE1-AS(r=-0.482,95%CI=-0.6820 to-0.2139.P=0.001).3.2 17A and sMRI indexesSpearman correlation analysis was used to analyze the correlation between 20 parameters of sMRI and the expression level of 17A in plasma exosomes of 48 subjects.Conclusion:This study is the first to investigate the correlation between BACE1-AS and 17A and MRI data of medial temporal lobe subregion.It is found that there is a negative correlation between the right amygdala volume and the expression of BACE1-AS in plasma exosomes in AD patients.We speculate that BACE1-AS may participate in amygdala atrophy in AD through exosome pathway.Part 4 The diagnostic value of BACE1-AS and 17A combined with sMRI parameters of medial temporal lobe for ADAs mentioned previously,we found that the plasma exosomal BACE1-AS and 17A expression levels were significantly increased in AD patients.Structural MRI analysis showed that the right entorhinal cortex volume,right entorhinal cortex thickness,left amygdala volume and right amygdala volume of AD patients were significantly reduced compared with the control group.These indexes can be used as potential diagnostic markers for AD.However,it is difficult for a single index to have high sensitivity and specificity at the same time.In order to improve the diagnostic efficiency,we use the joint diagnostic test and binary logistic regression model to explore the joint diagnosis of each index.4.1 Joint diagnostic testTwo differentially expressed BACE1-AS and 17A in AD and control and four parameters of MRI in medial temporal lobe subregion(right entorhinal cortex volume,right entorhinal cortex thickness,left amygdala volume and right amygdala volume)were analyzed by serial and parallel diagnostic tests respectively.4.1.1 BACE1-AS and 17AThe sensitivity,specificity,accuracy and Youden index for serial test were 59.09%,80.77%,70.83%and 0.399 respectively.The sensitivity,specificity,accuracy and Youden index for parallel test were 86.36%,46.15%,64.58%and 0.325 respectively.4.1.2 Four indexes of medial temporal lobe subregionThe sensitivity,specificity,accuracy and Youden index for serial test were 22.73%,100%,64.58%and 0.227 respectively,and 77.27%,69.23%,72.92%and 0.465 for parallel test respectively.4.1.3 BACE1-AS and four indexes of medial temporal lobe subregionThe sensitivity,specificity,accuracy and Yoden index for serial test were 22.73%,100%,64.58%,0.227,respectively.The sensitivity,specificity,accuracy and Yoden index for parallel test were 100%,0%,45.83%and 0.227 respectively.4.1.4 17A and four indexes of medial temporal lobe subregionThe sensitivity,specificity,accuracy and Youden index for serial test were 18.18%,100%,62.5%and 0.182 respectively.And they were 100%,30.77%,62.5%and 0.308 for parallel test respectively.4.1.5 The two lncRNAs and four indexes of medial temporal lobe subregionThe sensitivity,specificity,accuracy and Youden index for serial test were 18.18%,100%,62.50%and 0.182 respectively.They were 18.18%,23.08%,58.33%and 0.231 for parallel test respectively.4.1.6 BACE1-AS and volume and thickness of right entorhinal cortexThe sensitivity,specificity,accuracy and Youden index for serial test were 36.36%,96.15%,68.75%and 0.325 respectively,while they were 90.91%,42.31%,64.58%and 0.332 for parallel test respectively.4.1.7 BACE1-AS and right amygdala volumeThe sensitivity,specificity,accuracy and Youden index for serial test were 59.09%,88.46%,88.46%and 0.476 respectively,and for parallel test were 86.36%,61.54%,72.92%and 0.479,respectively.4.1.8 Bilateral amygdala volumeThe sensitivity was 45.45%,the specificity was 92.31%,the accuracy was 70.83%,the Youden index was 0.378 for serial test.And they were 81.82%,76.92%,79.17%,and 0.587 for parallel test.4.1.9 17A and Bilateral amygdala volumeThe series test were carried out,and the results showed that the sensitivity,specificity,accuracy and Youden index were 27.27%,96.15%,64.58%and 0.234,respectively;and were 95.45%,46.15%,68.75%and 0.416 for parallel test respectively.4.1.10 BACE1-AS and Bilateral amygdala volumeThe sensitivity,specificity,accuracy and the Yoden index were 40.91%.92.31%,68.75%and 0.332 for serial test.And for parallel test the sensitivity was 95.45%.the specificity was 53.85%,the accuracy was 72.92%,and the Yoden index was 0.493.4.1.11 17A and four indexes of medial temporal lobe subregionThe sensitivity,specificity,accuracy and Youden index were 18.18%,100%.62.5%and 0.182 respectively in series test.And the sensitivity,specificity,accuracy and Youden index were 100%,30.77%,62.5%and 0.308 respectively for parallel test.4.1.12 Volume and thickness of right entorhinal cortexThe sensitivity,specificity,accuracy and Youden index were 40.91%,92.31%,68.75%and 0.332 respectively for series test.And the sensitivity,specificity,accuracy,and Yoden index were 72.73%,73.08%,72.92%and 0.458 for parallel test.4.2 Establishment of regression modelThe binary logistic regression analysis was used to analyze the six indexes with difference between the two groups,and built the disease prediction model.There are three successful models.4.2.1 Volume and thickness of BACE1-AS combined with right entorhinal cortexModel 1:Logit(P=AD)=4.613+0.281 × bacel-as-1.375 x right entorhinal cortex thickness.ROC curve analysis showed that AUC was 0.747,sensitivity was 76.2%,specificity was 76.9%,accuracy was 76.6%,and Youden index was 0.531.4.2.2 BACE1-AS was combined with right entorhinal cortex volume and thickness,and age and gender were includedModel 2:Logistic(P=AD)=-2.013+0.389 × bacel-as-1.317 × right entorhinal cortex thickness+0.081 × age.ROC curve analysis showed that AUC was 0.819,sensitivity was 81%,specificity was 73.1%,accuracy was 76.6%,and Youden index was 0.541.4.2.3 17A combined with right entorhinal cortex volume and thickness,and age and gender were includedModel 3:Logit(P=AD)=-1.67-0.146 × 17a-1.789 × right entorhinal cortex thickness+0.108 × age.ROC curve analysis showed that AUC was 0.850,sensitivity 77.8%,specificity 76.9%,accuracy 77.08%,Youden index 0.547.Conclusion1.BACE1-AS and bilateral amygdala volume parallel test.17A and bilateral amygdala volume parallel test,had good sensitivity,up to 95.45%.and has a certain specificity,accuracy and authenticity is also good.The sensitivity of AD screening was 100%.but the specificity was low.2.Three logistic regression models for the diagnosis of AD were constructed,model 2 and 3 were significantly better than single index,and had obvious advantages.Innovation and significance1.This study found that there were significant differences in two lncRNAs of plasma exosomes and four sMRI indexes of medial temporal lobe in AD patients,which can be used as candidate markers for the diagnosis of AD.2.This study found for the first time that there was a negative correlation between the right amygdala volume and the expression level of BACE1-AS in AD patients.3.For the first time,series parallel test and logistic regression model were used to study the joint diagnosis of lncRNAs in plasma exosomes and multiple MRI indexes in medial temporal lobe subregion.Multiple diagnostic model markers were found,which can significantly improve the diagnostic efficiency of AD.4.This study provides a number of new,practical diagnostic biomarkers for AD,which is helpful for the early diagnosis and treatment of AD. |
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