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Objective:To investigate the role of plasma neurofilament light chain (NfL) in diagnosing and differentiating Parkinson's disease (PD) and multiple system atrophy-Parkinsonian subtype (MSA-P).Methods:Forty PD patients and 23 MSA-P patients admitted to Department of Neurology, Henan Provincial People's Hospital from June 2019 to December 2021 were recruited; 27 healthy subjects accepted physical examination during the same period were selected as controls. Ultrasensitive Simoa technology was used to measure the plasma NfL. Differences in clinical data and plasma NfL were compared among all subjects. Correlations of plasma NfL with clinical characteristics, such as disease course, Hoehn-Year (H-Y) staging, Unified Parkinson's Disease Rating Scale (UPDRS), Montreal Cognitive Assessment (MoCA), Scale for Outcomes in Parkinson's Disease for Autonomic Symptoms (SCOPA-AUT) and levodopa equivalent daily dosage (LEDD), were analyzed with Pearson correlations. Receiver operating characteristic (ROC) curve was used to analyze the value of plasma NfL in diagnosing and differentiating PD and MSA-P.Results:Compared with MSA-P group, PD group had significantly longer disease course and statistically lower scores of UPDRS-II and SCOPA-AUT ( P<0.05). The plasma NfL in MSA-P group, PD group and healthy control group was decreased successively ([37.69±10.47] pg/mL, [17.85±4.23] pg/mL, [12.86±3.14] pg/mL, respectively), with statistical differences ( P<0.05). In MSA-P patients, Pearson correlations showed positive correlation between plasma NfL and age ( r=0.442, P=0.035); and Partial correlations showed positive correlations between plasma NfL and scores of UPDRS-I and UPDRS-III ( P<0.05), and plasma NfL showed no significant correlation with H-Y staging, UPDRS-III, MoCA, LEDD or SCOPA-AUT scores ( P>0.05). In PD patients, Pearson correlations showed that plasma NfL was positively correlated with age ( r=0.342, P=0.031); partial correlations showed that plasma NfL was positively correlated with H-Y staging and UPDRS-III, and negatively correlated with MoCA scores ( P<0.05); plasma NfL showed no significant correlation with disease course, scores of UPDRS-I and UPDRS-II, LEDD, and SCOPA-AUT scores ( P>0.05). ROC curve showed that the area under the curve (AUC) of plasma NfL in diagnosing PD was 0.814 (95% CI: 0.712-0.920, P<0.001); AUC of plasma NfL in differentiating and diagnosing PD and MSA-P was 0.980 (95% CI: 0.954-1.000, P<0.001); AUC of plasma NfL in diagnosing MSA-P was 0.998 (95% CI: 0.993-1.000, P<0.001). Conclusions:Plasma NfL is correlated with severity of motor symptoms in MSA-P patients; plasma NfL is correlated with cognitive function and disease course in PD patients. Besides, plasma NfL has high sensitivity and specificity in differentiating PD and MSA-P, therefore, plasma NfL could serve as a biomarker to diagnosis and differentiate PD.
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Objective:To investigate the relationship between plasma phosphorylated α-synuclein (ps129-α-syn) and cognitive function in Parkinson disease (PD).Methods:This study recruited 90 PD patients who were hospitalized in the Department of Neurology, Henan province people's hospital from March 2019 to June 2020.Forty healthy middle-aged and elderly people with normal cognitive function who came to the hospital for physical examination were selected during the same period.Clinical characteristics and blood samples were collected.Patients with PD were classified into those with normally cognitive (PD-NC), mild cognitive impairment (PD-MCI), and dementia (PDD). The enzyme-linked immunosorbent assay was used to measure the plasma ps129-α-syn.Correlations between plasma ps129-α-syn and clinical characteristics such as disease duration, Hoehn-Yahr stage (H-Y), unified Parkinson's disease rating scale (UPDRS), Montreal cognitive assessment (MoCA), 14-item Hamilton anxiety rating scale (HAMA-14), the 24-item Hamilton depression rating scale (HAMD-24), levodopa equivalent daily dosage (LEDD), the scale of outcomes in Parkinson's disease for autonomic symptoms, SCOPA-AUT) were analyzed using Pearson or Spearman correlation analysis.Multiple linear regression analysis was used to evaluate the factors affecting the cognitive function of PD.Results:Plasma ps129-α-syn in PD patients was higher than that in healthy controls((19.44±8.93)μg/L, (10.78±5.87)μg/L, ( t=5.615, P<0.01). Plasma ps129-α-syn was higher in PD-MCI group((19.64±7.77)μg/L)and PDD group((23.79±9.47)μg/L) compared with that in PD-NC group((13.37±5.40)μg/L)( P<0.05). Plasma ps129-α-syn was positively correlated with H-Y ( r=0.404, P<0.01), UPDRS-Ⅲ( r=0.275, P=0.009), UPDRS-total ( r=0.211, P=0.046) and SCOPA-AUT( r=0.335, P=0.001). Plasma ps129-α-syn was negatively associated with MoCA ( r=-0.459, P<0.01). Multiple linear regression analysis suggested disease duration ( t=-4.618, P<0.01), ps129-α-syn( t=-3.792, P<0.01) and UPDRS-total ( t=-2.826, P=0.006) were independently associated with cognitive function.Plasma ps129-α-syn could discriminate between PD-NC and PD cognitive function impairment with an AUC of 0.7797 (95% CI: 0.686 3-0.873 2, P<0.01). Conclusions:Plasma ps129-α-syn is correlated with cognitive function and the severity of motor symptoms in PD patients, and have high sensitivity and specificity in diagnosing PD cognitive dysfunction.Therefore, plasma ps129-α-syn can serve as a biomarker to assess cognitive function in PD.
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Objective To investigate the effects of exercise on memory impairment in demented mice and possible molecular mechanisms.Methods Thirty Kunming nice were divided into a normal control group,a dementia group and a dementia plus exercise training group (exercise training group),10 mice/group. Dementia models were established by intraperitoneal injection of scopolamine.Exercise training was begun 30 min after the injection and lasted for a 6-week period. A water maze test was performed after the exercise training. Brain-derived neurotrophic factor (BDNF) expression and protein kinase (Akt) phosphorylation in the hippocampus were detected by Western blot analysis.Nitric oxide (NO) content and superoxide dismutase (SOD) activity in the hippocampus were also measured.ResultsDementia models were successfully induced as indicated by prolonged escape latency in the water maze test.After exercise training the escape latency had shortened significantly and hippocanpal BDNF expression and Akt phosphorylation had increased.NO content increased and SOD activity decreased after the injections,but these effects were partially reversed after exercise training.Conclusions Exercise can improve spatial memory significantly after scopolanine-induced dementia in mice.The increased hippocampal BDNF expression and Akt phosphorylation,increased SOD activity and decreased NO content may partially explain the behavior improvement induced by exercise.
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Objective To investigate platelet α and β secretase activities and the amounts of platelet soluble fragment of APP (sAPPα) produced by α-secretase in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD).Methods The neurological functions of 48 nondemented patients,42 MCI and 40 AD patients were evaluated by neuropsychological examinations.The platelet α and β secretase activities and sAPPα production in each group were measured by fluorescence and Western blotting analysis respectively.Results The α secretase activities in non-demented,MCI and AD group were 100.0％ ± 10.6％,78.2％ ± 9.4％ and 61.8％ ± 7.2％ respectively.As compared with nondemented group,the α secretase activities in MCI and AD group were decreased (F =22.935,P =0.001).The α secretase activity in AD group was significantly lower than MCI group.The β secretase activities in non-demented,MCI and AD group were 100.0％ ± 11.2％,145.8％ ± 12.7％ and 189.8％ ± 14.2％respectively.The β secretase activities in MCI and AD group were significantly higher than that in nondemented group (F =16.368,P =0.001).The β secretase activity in AD group was significantly decreased as compared with MCI group.The sAPPα amounts in MCI group and AD group were all decreased as compared with that in control group; the sAPPo amount in AD patients was significantly decreased as compared with that in MCI group.Conclusions The platelet α secretase activity and its production sAPPα in MCI and AD patients are decreased,while β secretase activity is increased,as compared with that in control group; the altered α and β secretase activities may participate in the pathogenesis of MCI and AD patients and may have diagnostic potential for them.