| Objective: To explore the varieties of cerebrospinal fluid NfL concentration in patients who were diagnosed as a-MCI and AD under the pathological background of Aβ and tau pathology,and its correlation with MRI image markers like gray matter volume,white matter volume and the ratio of them.Methods: This study included 40 patients who were diagnosed with probable AD and 12 patients were diagnosed with a-MCI in the Cognitive Specialty of the Provincial Hospital Affiliated to Anhui Medical University from March 2019 to September 2020,There were 28 controls were concluded,and a total of 80 subjects.The basic clinical data of the subjects were collected,and some metabolic indicators like blood lipid were detected.The cerebrospinal fluid samples were collected,and the concentrations of NfL,T-tau,P-tau,Aβ40 and Aβ42 in cerebrospinal fluid were measured.We measured the volume of gray matter,white matter and white matter hyperintensity According to MRI of all subjects based on the analysis of region of interest(ROI).All the indexes were statistically analyzed.Results: 1.General data: The average age of the control group was 60.07±7.18 years old;In a-MCI group,the average of age was 63.00±7.36 years old;The cases in the AD group with an average of 64.44 ± 4.11 years old.Age,gender,education level and related clinical indicators,such as white blood cell count,blood glucose,blood lipid,cerebrospinal fluid protein and other metabolic and inflammatory indicators among the three groups were compared,and no significant differences were shown.2.Neuropsychological score: MMSE score in the control group,a-MCI group and AD group showed a downward trend,the average score was 27.41±2.75,21.56±3.39,13.19±5.60,with statistical difference.Mo CA score in the control group,a-MCI group and AD group also gradually decreased,the average score was 23.78±3.79,15.80±4.90,8.86±5.11(P<0.001).ADL scores in the three groups also were showed as a significant upward trend(P<0.001).3.CSF markers: T-tau concentration showed an increasing trend in the control group,a-MCI group and AD group,which were 192.19±83.45pg/m L、453.96±272.17pg/m L、658.02±412.59pg/m L respectively;P-tau concentration showed similar change,The mean values of the three groups were 45.69±13.67pg/ml,71.99±23.66pg/ml and 89.49±41.11pg/ml.On the contrary,the average concentration of Aβ42 in three groups were 467.18±181.94pg/ml,369.08±239.92pg/ml,285.45±76.67pg/ml respectively;the differences of these three markers among the three groups were statistically significant(P<0.001);there was no significant difference in the concentration of Aβ40 in cerebrospinal fluid(P>0.05);the level of NfL in cerebrospinal fluid of normal control subjects was significantly lower than that of a-MCI group and AD group The average concentration of patients was 1216.19 ± 1008.29pg/ml in control group,1698.20 ± 965.74pg/ml in a-MCI group,2542.99 ± 1699.31pg/ml in AD group,This growth trend is statistically different(P<0.001).4.Magnetic resonance biomarkers: the average volumes of gray matter and white matter were 607.39±37.00mm3 and 538.76±53.97mm3 in control group,555.66±39.72mm3 and 497.69±67.82mm3 in a-MCI group and 539.52±78.81mm3 and 426.31±108.59mm3 in AD group respectively.The gray matter to white matter ratio in patients with a-MCI was significantly lower than that in patients with AD,like the white matter hyperintensity in a-MCI group(P<0.05).5.Ordered multiple regression analysis showed that NfL concentration in CSF was positively correlated with a-MCI and AD(OR=1.001,P=0.012),while Aβ42 concentration in CSF was negatively correlated(OR=0.994,P=0.017).In addition,NfL concentration in CSF was negatively correlated with MMSE and Mo CA scores(R =-0.276,-0.259),and positively correlated with ADL score(R=0.260)in Pearson analysis.And CSF-NfL correlated with T-tau and P-tau(R=0.345,0.324)in CSF positively;the correlation analysis between the concentration of NfL in CSF and the MRI markers showed that there was a significant positive correlation between NfL and gray matter to white matter volume ratio(R=0.265),and the ROC curve showed that the diagnostic value of the combination of NfL and gray-to white matter ratio was higher than that of single diagnosis,the area under the curve was 81.5%.6.The ordered multiple regression analysis of MRI structural markers to groups showed the OR value of the gray matter to white matter ratio was highest(OR>20);the ROC curves of Aβ42,gray matter volume,white matter volume and their combined diagnosis of cognitive impairment were drawn.The results showed that the combined diagnosis value was significantly higher,and the area under the curve was 90.3%.Conclusion: This study suggests that CSF NfL may be used as a marker for the diagnosis and monitoring of the severity of AD,which is related to tau pathology;MRI gray matter white matter volume ratio and white matter high signal may be used as sensitive indicators for the aggravation of AD,which is related to NfL and tau pathology,and can be used in the diagnosis of AD. |
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