Correlation between prion protein gene codon 129 polymorphism and late-onset Alzheimer's disease

BACKGROUND： Studies addressing the correlation between prion protein gene codon 129 polymorphism, Alzheimer＇s disease, and cognitive disorders have mainly focused on Caucasians. However, prion protein gene codon 129 polymorphism is thought to also affect the Chinese Han and Wei populations. OBJECTIVE： To analyze the differences of prion protein gene codon 129 distribution among the elderly Chinese Han, East Asian, and Caucasian populations, and to study the correlation between prion protein gene codon 129 distribution and late-onset Alzheimer＇s disease. DESIGN, TIME AND SETTING： A gene polymorphism analysis was performed in the Institute of Geriatrics, General Hospital of Chinese PLA between January 2006 and January 2007. PARTICIPANTS： A total of 152 elderly Chinese Han people were selected from the Beijing Troop Cadre＇s Sanitarium. Among them, 60 patients with late-onset Alzheimer＇s disease, with a mean age of （82 ± 7） years （range 67-94 years） and disease course of （5.9 ± 4.4） years, comprising 44 males with a mean age of （83 ± 7） years and 16 females with a mean age of （78 ±7） years, were selected for the case group. An additional 92 healthy elderly subjects, with a mean of （76 ± 9） years （range 60-94 years）, comprising 76 males with a mean age of （77 ± 9） years and 16 females with a mean age of （70 ± 8） years, were selected for the control group. There were no significant differences in age and gender between the two groups （P〉 0.05）. METHODS： DNA was extracted from peripheral blood leukocytes using routine phenol/chloroform methodology. Prion protein gene codon 129 potymorphism and ApoE polymorphism were measured using PCR-restriction fragment length polymorphism. The ApoEε allele was considered the standard for analyzing correlations between prion protein gene codon 129 polymorphism and late-onset Alzheimer＇s disease. MAIN OUTCOME MEASURES： Prion protein gene codon 129 distribution; correlation between genotypic frequency and allele frequency of prion protein gene codon 129 with Alzheimer＇s disease; relationship between methionine/methionine genotype of priori protein gene, ApoEε4 allele, gender, and age of Alzheimer＇s disease patients. RESULTS： Methionine/methionine genotypic frequency of prion protein gene codon 129 was 94.08% in the Chinese elderly population, and the methionine/valine genotypic frequency was 5.92%. However, valine/valine homozygotes were not determined. There was no significant difference in prion protein gene codon 129 polymorphism between the Chinese elderly and East Asian populations （P〉 0.05）. However, there was a significant difference between the Chinese elderly and the Caucasian population （P 〈 0.05）. The methionine/methionine genotype for the positive and negative ApoEε4 alleles was a risk factor for increased incidence of Alzheimer＇s disease, but there was no significant difference between the positives and the negatives （odds ratio = 1.33, 95% confidence interval = 0.32-6.49, P〉 0.05）. CONCLUSION： Prion protein gene codon 129 distribution in the Chinese elderly was different from the Caucasian population, which suggested that the methionine/methionine genotype of prion protein gene codon 129 negatively correlated with late-onset Alzheimer＇s disease.

血清/脑脊液中抗LGI1/CASPR2抗体均阳性Morvan综合征1例报道并文献复习

本文报道血清及脑脊液富亮氨酸胶质瘤失活蛋白1(LGI1)和接触蛋白相关样蛋白2(CASPR2)抗体四阳性导致的典型Morvan综合征1例患者的临床特点及预后。对该Morvan综合征患者行详细的病史询问和体格检查、多次脑脊液检查、头颅影像学、电生理检查以及预后进行分析。临床特点:患者青年女性, 39岁, 首发症状表现为四肢无力, 病程中主要症候包括发作性肢体疼痛、憋喘、瘙痒、肌颤搐、癫痫、记忆力减退、烦躁、淡漠、顽固性失眠、流涎、出汗异常。实验室检查:电解质示低钾血症(2.7~3.1 mmol/L)、低钠血症(130~136 mmol/L);血气分析示低氧血症(氧分压50%~70%)。甲状腺功能:总甲状腺腺素(TT4)207 nmol/L、甲状腺过氧化物酶抗体(TPO-Ab)15.3 IU/ml、甲状腺球蛋白抗体(TG-Ab)16.9 IU/ml;血清和脑脊液抗LGI1/CASPR2抗体呈四阳性, 其他自身免疫相关脑炎及副肿瘤综合征相关抗体均阴性。头颅MRI未见异常;脑电图轻度异常;肌电图示左股四头肌运动单位电位电压略高。治疗及预后:激素+丙种球蛋白+吗替麦考酚酯片联合治疗, 患者临床症状完全缓解。治疗前后认知功能评分:治疗前蒙特利尔认知评估量表(MoCA)/简易智力状态检查(MMSE)(16分/24分)、治疗后MoCA/MMSE(26分/29分)。Morvan综合征血清/脑脊液中LGI1/CASPR2抗体四阳性罕见, 但临床症候典型, 尽早免疫治疗效果显著。