通过对疾病特异性病理蛋白的标记，分子成像能够对神经退行性疾病患者进行活体显像，为神经退行性疾病的诊断、鉴别诊断、治疗方案的确定以及机制研究等提供客观依据。.

"寿比南山"是中国家庭对长辈的美好祝愿,也是祈盼与老人共享"福如东海".但随年龄增长而日益增多的"阿尔茨海默病"(旧译为"老年性痴呆")患者却颠覆了整个家庭的生活轨迹.

神经系统变性疾病主要包括阿尔茨海默病（Alzheimer，AD ）病、额颞叶萎缩（代表病Pick 病）、帕金森综合征（PDS）、多系统萎缩（MSA）、肌萎缩侧索硬化（ALS）、进行性核上性麻痹（PSP）等。神经系统变性疾病患者常有睡眠障碍的主诉，对临床睡眠医生来说有关这些疾病的相关基础知识是必不可少的。下面对主要的神经变性疾病有可能出现的睡眠问题进行简述。

Objective To make the foundation of further research on the mechanism of AD,we studied the differential proteins in temporal lobes between Alzheimer disease(AD) patients and normal elderly individuals.Methods Human temporal lobes in 12 autopsied individuals were obtained through the Tissue Bank of the Institute of Geriatrics,Chinese PLA General Hospital.They were divided into two groups :normal elderly individuals(n= 6)and Alzheimer' s disease patients(n= 6).We carried out the isobaric tags for relative and absolute quantitation(iTRAQ) coupled with two‐dimensional liquid chromatography‐tandem mass spectrometry(2D LC‐MS/MS) to identify the main differential proteins of the temporal lobe tissue in AD individuals versus the normal elderly individuals.Results Among the 3071 proteins identified, a total of 146 proteins were differentially expressed in AD patients versus normal elderly individuals.We comparatively analyzed the total 146differential proteins using the bioinformatics analysis and identified 7 candidate proteins of interest.ConclusionsThrough the technique of iTRAQ, we can select some differential proteins related with AD, quickly and effectively,which provide the basic data for the effective prevention or targeted therapy of AD.

Objective To study the alteration of thalamus function connectivity pattern in patients with mild cognitive impairment( MCI) during a one year follow-up. Methods In the present study,neuropsychological tests and functional connectivity analysis based on resting state functionalmagneticresonanceimaging(fMRI)wereevaluatedin13MCIsubjects(age74.5±8.7years,gender8M/5F)bothatthebaselineand one year later. Then a correlation analysis was performed between the strength of functional connectivity of the identified regions and various clinical variables for evaluating the relationships between the strength of functional connectivity and the cognitive abilities of the MCI patients. Results Compared to the baseline,MCI patients showed decreased functional connectivity between the left thalamus and several regions of brain including left inferior parietal cortex,left putamen and right cerebellar posterior lobe( VIIB). Decreased functional connectivity was also detected between the right thalamus and left putamen. There were no correlations between alteration on the functional connectivity and changes of cognitive function. Conclusion Functional connectivity between the thalamus and several brain regions which were involved with high level cognition is impaired over time in the MCI patients. Our results provided useful information for research on the pathophysiological mechanism of the conversion from MCI to AD.

由于社会文明的发展以及医学技术的不断进步,世界各国均呈现普遍的老龄化趋势,而中国老年人口,特别是高龄人口的比例和数量的快速增长已成为21世纪我国人口结构的重要特征。目前我国老年人口已突破1.6亿,与日本人口总量相近,且据专家预测,至2050年,中国≥65岁老年人口占总人口的比例将高达30.4%,而其中≥80岁的高龄老人将超过1亿,占当时老年人口比例的23%!不言而喻,这样一个庞大的老年及高龄群

Objective To evaluate the genetic factors for sporadic Alzheimer's disease(SAD) among a Chinese population in Beijing. Gene polymorphisms was studied: apolipoprotein E,ps-1 gene E318G missense mutation,alpha(2)-macroglobulin gene Val1000/Ile1000,mtDNA4336G mutation and methylene tetrahydro-fulek reduclase (MTHFR) C677T mutation. Methods The polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)technique was used to analyze the genotype of 127 SAD patients and 138 non-dementia elderly controls. Results There was a significant difference in the frequency of apoE allele gene between SAD and control group. The freguencies with 2 of apoE4 ,1 of apoE4 and none of apoE4 in SAD were 2.4%,18.1%,79.5% respectively,and in normal control were 0.7%,10.1%,89.2% respectively. mtDNA4336 mutation and ps-1 E318G missense mutation were not found in either Alzheimer's disease or age-matched controls. The frequency of A2M Val1000 (GTC)/Ile1000 (ATC),G/G genetype was 0.02 in SAD and 0.01 in NC . The frequency of MTHFR C677T mutation was 46.3% in SAD and 43.8% in NC respectively, The mutation frequency of cases was not significantly increased than that of controls. Conclusions Our study indicates that apoEe4 allele gene is risk factor for SAD.

Objective To study the implicit and explicit memory in the patients with amnestic mild cognitive impairment (MCI).Methods The study employed a cross-sectional design.Twenty patients with MCI (MCI group) and 20 normal elderly(control) were examined using a set of psychological tests including word free recall, recognition, free association and degraded word naming test.Results The group of forgetful-style MCI had semantic priming effect and apperceptive priming effect. In addition, this group also had a decline in explicit memory as compared with controls,however there was no significant difference in the implicit memory.Conclusion Patient with forgetful-style MCI exhibits a decline in explicit memory,but the implicit memory is relatively complete. The dualnature of memorial function provides theoretical basis for the rehabilitative training of MCI patients.

Objective To research a reliable hemo-experimental method to diagnose Alzheimer disease.Methods The patients were divided into three groups.Alzheimer group consisted of 11 cases (67-82 years old,7 males and 4 females).The multiple infarct dementia (MID) group consisted of 13 cases (62-80 years old,8 males and 5 females).The old control group consisted of 53 cases (60-79 years old,25 males and 28 females).Both the erythrocyte electrophoresis assay and the serum anti-brain autoantibody assay were used.Alzheimer disease was diagnosed positively only when the both assays were positive in one patient.Results The positive rates of Alzheimer group,MID group and the old control group were 36.36% (P0.01),15.38% and 1.89% respectively.Conclusion It is suggested that the combined application of the erythrocyte electrophoresis assay and the serum anti-brain autoantibody assay is a good method for diagnosis of Alzheimer disease.

目的研究无神经系统疾病的正常增龄患者神经元及毛细血管密度的相对变化,并与阿尔茨海默病(Alzheimer's diseasea,AD)患者比较,探讨在脑老化及痴呆防治中对血管因素进行干预的意义.方法收集无神经系统疾病的正常病例脑标本28例(23～100岁)及AD尸检脑标本6例,应用荆豆凝集素(Ulex europaeus agglutinin,UEA)及甲苯胺蓝等染色显示无神经系统病史及神经病理改变的尸检病例(正常病例)额叶、枕叶、壳核、海马CA3区及AD患者海马的神经元、毛细血管形态,应用图像分析技术测定各部位神经元与毛细血管密度,分析二者比值与年龄之间的相关性.结果正常增龄病例额叶、枕叶、壳核神经元与毛细血管数目及面积之比与年龄呈正相关.正常高龄病例(≥75岁)与AD病例海马部位两者之比较差异无显著性意义.结论脑老化中毛细血管退变可能是脑组织代谢下降、功能减退的原因之一;对血管因素的干预在脑老化及AD防治中具有重大意义.

Objective To investigate the distribution of calbindin D 28K (CaBP) in senile hippocampus and to analyse the effect of CaBP on change of physiology and pathology of neurons during aging.Method The hippocampus samples of left cerebral hemisphere were processed with pathological routine and sliced after autopsy in 12 cases over 60 years of age without brain disorders.Distribution of CaBP in hippocampus CA1 and CA3 areas was observed with immunohistochemical ABC staining.Results CaBP immunoprecipitates were shown to appear in neuronal cytoplasm.CaBP-immunoreactive cells were more numerous in CA1 of hippocampus than in CA3.Conclusion These data suggest that CaBP might play an important role in function of hippocampus.

Objective To investigate the symptoms and prognosis of central nervous system (CNS) involvement of systemic lupus erythematosus (SLE). Methods The clinical data of 98 SLE patients with CNS involvement were retrospectively reviewed. Results The clinical data of 98 SLE patients with CNS involvement was classified as cognitive impairment (41%), seizure(44.9%), headache(8%) and cerebral vascular infarction(6%). The prognosis of cerebral vascular infarction group was significantly worse than the other three groups. The incidence of cognitive impairment in SLE was 41% with the reversible rate of 90%. Conclusion The prognosis is significantly related to clinical feature in CNS. The cognitive impirement in SLE with CNS involvement is common and generally reversible.

Objective To investigate the changes of regional cerebral blood flow (rCBF) in acute stage of hypertensive cerebral hemorrhage (HCH).Methods Thirty patients underwent CT within 24 hours and SPECT within 72 hours after onset of HCH.Hematoma volumes and edema volumes were calculated using CT,semiquantitative rCBF and flow deficit volumes(FDV) were measured using SPECT.SPECT graded scale,neurological grading within 72 h after onset and Barthel Index (BI) at 4th week after onset were evaluated.Results (1) Brain edema formed within 24 hours after onset of HCH.There was strong linear correlation between edema volume and hematoma volume(r=0.8685,P0.01)and also FDV (r=0.3562,P0.01).(2) rCBF was significantly reduced in acute HCH.(3) Linear correlation between SPECT graded scale and neurological grading was significant (r=0.87,P0.01).There was also negative linear correlation between SPECT graded scale and Bathel Index (r=-0.82,P0.01).Conclusions (1) There was brain edema formation within 24 hours after onset of HCH;(2)The major factors affecting rCBF were hematoma volume and location;(3) Ischemia penumbra also existed in HCH.

Objective To investigate the effects of defibrase on the focal cerebral ischemia-reperfusion injury in rats and to discuss its possible mechanisms.Methods 156 healthy male Wistar rats were divided randomly into defibrase group and saline group.The rats were subjected to middle cerebral artery occlusion with intraluminal filament occlusion and intraperitoneal injection of 8 U/kg defibrase simultaneously.TTC staining and SP immunohistochemistry were applied to examine glial fibrillary acidic protein.Cerebral infarction volume ratio at different time and changes of neurons were measured.The number,circumference and integral spectrophotometric value of astrocyte were also observed.Results The cerebral infarction volumes of defibrase group were smaller significantly than those of saline group.Reactive astrocyte's number,circumference and spectrophotometric value of defibrase group were much greater,and haemorrhagic infarction incidence in defibrase group was significantly lower than those of saline group.Conclusions Defibrase does have protective effect against cerebral ischemia-reperfusion injury in rats.Proliferation of reactive astrocyte and alleviation of endothelial cell injury may be involved in the mechanisms of protection.

ObjectiveTo investigate the intensity of degrading plasma fibrinogen(FIB) and the therapeutic effectiveness of defibrase on treating cerebral ischemia by different administrated ways. MethodsIntraluminal suture method was used to develop reversible middle cerebral artery occlusion (MACO). 154 healthy male Wistar rats were randomized into 2 groups. The rats in intravenous treatment group were injected defibrase intravenously at 0.5,3,6,9,12hours after MACO,while the rats in coeliac treatment group were injected defibrase by abdominocentesis. Meanwhile the control group received normal saline. All rats were killed at 24 hours after MCAO. The thrombus in middle cerebral artery (MCA) and cerebral infarction were examined microscopically in HE stained sections. Infarction volume was measured by using 2,3,5-triphenyltetrazolium chloride staining. 24 rats were selected randomly and injected defibrase by intravenous injection and abdominocentesis. Plasma FIB was measured before and after injection 1,3,6,12,24h by intravenous haemospasia. ResultsPlasma FIB was significantly reduced in intravenous treatment group, and it was lowerest in 3h after intravenous treatment.Clinical Neurological Deficits Scale and infarction volume was significantly reduced in intravenous treatment group than saline control group and coeliac treatment group.There was improvement in Clinical Neurological Deficits Scale in coeliac treatment group compared with that of saline control group, but there was no statistically significant differences at infarction volume.Clinical Neurological Deficits Scale and infarction volume was statistically significant differences in intravenous treatment group at 0.5,3 hours after MCAO. There were no statistically significant differences in intravenous treatment group at 6, 9,12 hours after MCAO.Conclusions Defibrase can reduce the infarction volume in cerebral ischemia early stage.