载脂蛋白E基因多态性与Alzheimer病

目的：探讨广东地区Ａｌｚｈｅｉｍｅｒ病（ＡＤ）患者与ａｐｏＥε４之间的关联性及性别的影响。方法：应用聚合酶链反应－限制性片段长度多态性分析（ＰＣＲ－ＲＦＬＰ）的技术对４４例晚发性散发性ＡＤ患者、３７例非痴呆老年人的ａｐｏＥ基因进行分型。结果：ａｐｏＥε４与晚发性ＡＤ有显著的关联;携带１个或１个以上ε４者与无ε４携带者比较,相对危险度（ＯＲ值）为４．０８,且随ε４基因剂量增加,ＡＤ的患病率上升,发病年龄明显提前（Ｐ＜０．０１）;ＡＤ患者不同性别之间ａｐｏＥε４基因型频率和等位基因频率无显著性差异（Ｐ＞０．０５）。结论ａｐｏＥε４是晚发性ＡＤ发病的危险因素;ＡＤ患者的性别因素与ａｐｏＥε４无相关性。     

Apolipoprotein E polymorphism, Alzheimer's disease and vascular dementia among elderly Finnish men

An association between late-onset Alzheimer's disease, vascular dementia and the common polymorphic alleles of the gene coding for apolipoprotein E, ɛ2, ɛ3 and ɛ4, was assessed in a population sample of 393 elderly Finnish men aged 70 to 89 years. Of them, 7%, suffered Alzheimer's disease and 3% had vascular dementia. Among those who suffered Alzheimer's disease, there was a statistically significant excess of the ɛ4 allele. No such an association was observed between the apolipoprotein E alleles and vascular dementia. We conclude that the apolipoprotein E polymorphism confers information about a risk of Alzheimer's disease in this population sample of elderly Finnish men.     

Apolipoprotein E polymorphism in Japanese patients with Alzheimer''s disease or vascular dementia.

Apolipoprotein E (ApoE) plays a key part in lipid metabolism both in the liver, and in the CNS. To clarify the association of ApoE polymorphism with Alzheimer's disease and vascular dementia in Japan, 13 patients with early onset (age > or = 65) sporadic Alzheimer's disease, 40 patients with late onset (age < or = 65) sporadic Alzheimer's disease, 19 patients with vascular dementia, and 49 non-demented control subjects were analysed. The results showed a significantly increased frequency of the epsilon 4 allele in the patients with late onset sporadic Alzheimer's disease (0.25), but not in the patients with early onset sporadic Alzheimer's disease (0.04) or in the patients with vascular dementia (0.13) compared with controls (0.09). The raised frequency of the epsilon 4 allele in the patients with late onset sporadic Alzheimer's disease was of a lower magnitude than that in United States and Canadian studies. This may in part be due to a lower epsilon 4 frequency in the normal Japanese population and reflect the lower morbidity from Alzheimer's disease in Japan.     

Alzheimer病和血管性痴呆患者载脂蛋白E基因多态性分析

探讨ApoE多态性与Alzheimer病（AD）和血管性痴呆（VD）的关系。方法：应用PCR—RFLP技术分析25例AD,30例VD及40例对照组人群的ApoE基因型。结果：与对照组相比较,AD和VD患者ε3频率降低（P＜0．05）,ε4频率升高（P＜0．05）,两组患者间各等位基因频率差异无统计学意义（P＜0．05）。结论：ApoE多态性与AD和VD的发病机制相关,其在这两种疾病中的作用相似。     

Apolipoprotein E and intronic polymorphism of presenilin 1 and alpha-1-antichymotrypsin in Alzheimer's disease and vascular dementia

Apolipoprotein E (ApoE) genotypes, presenilin 1 (PS-1) and alpha(1)-antichymotrypsin (ACT) polymorphism and the association of the genotypes were examined in patients with Alzheimer's disease (AD, n = 121) or vascular dementia (VD, n = 68) in comparison with elderly controls (n = 125). The frequency of the ApoE epsilon 4 allele was significantly increased both in late-onset AD (0.35) and in VD (0.17); the frequency of ApoE epsilon 2 was significantly reduced in AD, but it was similar in VD and controls. The presence of the allele 1 of PS-1 intronic polymorphism was not associated with AD or VD and was not influenced by the ApoE genotypes. Also, the frequency of allele A of the intronic polymorphism of ACT was similar in AD, VD and controls and it was not altered by ApoE or PS-1 genotypes. The results confirm the association between ApoE epsilon 4 and AD and indicate an increase in ApoE epsilon 4 in Vd, too. A potential protective role of ApoE epsilon 2 is also suggested for late-onset AD but not for VD. No association was shown between ACT allele A and PS-1 allele 1 in AD or VD.     

Apolipoprotein E polymorphism in ischemic cerebrovascular diseases and vascular dementia patients in Taiwan

This study aims to clarify the association between apolipoprotein E gene (ApoE) polymorphism, ischemic cerebrovascular diseases (ICVD) and vascular dementia (VaD) in Taiwan Chinese. 277 patients with ICVD, 49 patients with probable VaD and 112 controls were recruited for this study. Distributions of ApoE epsilon4 carriers and allele frequencies were 28.5 and 14.5% for patients with ICVD, 20.4 and 10.2% for patients with VaD, whereas these values were 22.9 and 11.6% for controls. Distributions of ApoE epsilon2 carriers and allele frequencies were 10.1 and 5.2% for ICVD patients, 6.1 and 3.1% for VaD patients, but 12.5 and 8.0% for controls. There were no differences between ICVD patients and controls, or VaD patients and controls in their epsilon4 carriers. Those patients aged 65 and under, carrying the epsilon2 allele, had a lower risk of developing ICVD and VaD than did their counterparts. These findings suggest that ApoE epsilon4 plays no significant role in the development of ICVD and VaD, but that ApoE epsilon2 has a protective effect with regard to the development of ICVD and VaD for Taiwan Chinese below the age of 65.     

Apolipoprotein E in patients with dementia of the Alzheimer type and vascular dementia

The phenotypes of apolioprotein E (ApoE) in the plasma of patients with dementia of the Alzheimer type (DAT) and vascular dementia (VD) were determined by the isoelectric focusing method. The ApoE mRNA level in the skin fibroblasts was also determined by the Northern blot analysis. As compared with the control subjects, the frequency of the ApoE ε4 allele was significantly higher in the DAT group as well as the VD group, but was not significantly different in the cerebrovascular disease without dementia (CVD) group. The skin fibroblast ApoE mRNA level in the DAT group and the VD group was significantly lower than that in the control group. These findings suggest that the phenotype of ApoE is associated with DAT and VD, and that the lower level of ApoE mRNA may play an important role in the development of DAT as well as VD.     

Apolipoprotein E polymorphism and behavioral and psychological symptoms of dementia in patients with Alzheimer disease

The aims of this study were to identify subsyndromes of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer disease (AD), and to investigate whether the apolipoprotein E (ApoE) gene confers a risk of distinct BPSD subsyndromes. BPSD of 96 patients with AD were assessed using the Neuropsychiatric Inventory. Factor analysis with principal component analysis and varimax rotation was used to construct the BPSD subsyndromes. ApoE genotypes were determined using the TaqMan technology. The results showed that the 5 subsyndromes can be determined, including: agitation/aggression-delusion, euphoria-disinhibition, depression-apathy, hallucination-nighttime behavior, and appetite. ApoE ε4 carriers had higher factor scores in the agitation/aggression-delusion subsyndrome. We demonstrated that ApoE ε4 confers a higher risk for the subsyndrome of agitation/aggression delusion in AD.     

Apolipoprotein E genotypes in hospitalized elderly patients with vascular dementia

BACKGROUND: Polymorphism in the apolipoprotein E (APOE) gene is the major genetic risk factor associated with late-onset Alzheimer's Disease (AD). However, it is still unclear if a relationship exists between the APOE epsilon4 allele and vascular dementia (VaD) in elderly subjects. OBJECTIVES: To evaluate the prevalence of APOE alleles in elderly patients with VaD compared to AD patients and to control subjects with no cognitive impairment (NoCI). PATIENTS AND METHODS: We evaluated 396 consecutive patients aged > or =65 years with definite or suspected cognitive impairment with a clinical (Mini-Mental State Examination, Clinical Dementia Rating, Geriatric Depression Scale), functional (Activities of Daily Living, Instrumental Activities of Daily Living), comorbidity (Cumulative Illness Rating Scale) and instrumental (CT scan, NMR) assessment. Diagnosis of dementia was made according to NINCDS-ADRDA and NINDS-AIREN Work Group and the DSM-IV. APOE genotypes were analyzed by a recently described method resulting in positive/negative chain reaction products for each APOE genotype. Statistical analysis was carried out using the Pearson chi(2), the Kruskal-Wallis test and the ANOVA post hoc comparisons. RESULTS: A total of 287 elderly patients (males = 138, females = 149, mean age = 77.8 +/- 6.9 years, range = 65-98) with diagnoses of VaD (n = 97), AD (n = 82) or NoCI (n = 108) were included in the study. A significantly higher APOE epsilon4 allele frequency was observed in AD patients compared to VaD and/or NoCI subjects, while no differences were found between VaD patients and subjects with NoCI (AD = 24.3%, VaD = 10.3, NoCI = 8.7, p < 0.05). Furthermore, a significantly lower APOE epsilon3 allele frequency was observed in AD patients compared to VaD and/or NoCI subjects but not between VaD and NoCI patients (AD = 71.3%, VaD = 80.9, NoCI = 83.4, p < 0.05). No significant differences were observed in the APOE epsilon2 allele (VaD = 8.8%, AD = 4.4, NoCI = 7.9, p = n.s.) among the 3 groups. CONCLUSIONS: In this population, the frequency of the APOE epsilon4 allele is lower in VaD than in AD.     

Presenilin-1 polymorphism in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia in Japanese population

We investigated the genetic association between intronic polymorphism in Presenilin-1 (PS-1) gene and patients with various types of dementia such as Alzheimer's disease (AD), vascular dementia (VD) and alcohol associated dementia (ALD), in Japanese population. Homozygosity for allele 1 of the PS-1 polymorphism was significantly increased in late-onset sporadic AD, but not in early-onset sporadic AD, familial AD, VD and ALD. When late-onset sporadic AD patients were divided on the basis of apolipoprotein E (APOE) genotype, homozygosity for the allele 1 of the PS-1 polymorphism was significantly increased in patients with late-onset sporadic AD without APOE εe 4 allele, but not in those with APOE εe 4 allele. Intronic mutation in PS-1 gene may be specific and one of the genetic risk factor for late-onset sporadic AD.     

Estrogen receptor gene polymorphisms in patients with Alzheimer's disease, vascular dementia and alcohol-associated dementia

The association between the estrogen receptor (ER-alpha) gene and dementia was examined in 223 patients with Alzheimer's disease (AD), 66 with vascular dementia (VD), 17 with alcohol-associated dementia (ALD) and 134 healthy elderly control subjects. The PvuII and XbaI restriction fragment length polymorphisms of the ER-alpha gene were represented as Pp (PvuII) and Xx (XbaI), with capital letters signifying the absence of restriction sites and small letters the presence of restriction sites. We found that the frequency of the ER-alpha gene P allele and X allele in the late-onset AD (LOAD) group (P allele was 0.51, X allele was 0.30) was significantly higher than that in controls (P 0.38, p < 0.01; X 0.20, p < 0.01), and that the frequency of the ER-alpha gene P allele and PP genotype was significantly different between apolipoprotein E epsilon4 carriers and noncarriers in LOAD. These findings suggest that the genotype of the ER-alpha gene may be specific in LOAD, and that the ER-alpha gene was an additional risk for LOAD.     

载脂蛋白E基因多态性与Alzheimer病和血管性痴呆的关系

目的 探讨载脂蛋白E(ApoE)基因多态性与Alzheimer病(AD)和血管性痴呆(VD)的关系.方法 用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测79例AD患者(AD组)、85例VD患者(VD组)及156名健康老年人(正常对照组)ApoE基因型和等位基因频率.结果 ApoEε3/ε4基因型及ε4等位基因频率AD组分别为25.3%及17.7%,VD组分别为25.9%及20.5%,正常对照组分别为10.9%及5.7%;AD组及VD组ApoEε3/ε4基因型及ε4等位基因频率显著高于正常对照组(均P＜0.01).结论 ApoEε4等位基因可能是AD和VD共同的危险因素.     

载脂蛋白E基因多态性和脑梗死关系的研究

目的探讨载脂蛋白E基因(ApoE)多态性与脑梗死的关系.方法采用病例-对照研究,对379例脑梗死患者和351例对照组进行研究.采用聚合酶链式反应-限制性片段长度多态性方法测定ApoE基因多态性.结果脑梗死组ApoE基因型频率E3/3、E3/4、E3/2、E2/4和E4/4型分别为72.3%、14.5%、11.6%、0.8%、0.8%.在脑梗死组中未发现E2/2.E2/2在脑梗死组和对照组之间有显著性差异(P＜0.05.)结论ApoE2/2对脑梗死可能具有保护作用.     

Apolipoprotein E gene polymorphism, total plasma cholesterol level, and Parkinson disease dementia

BACKGROUND: Apolipoprotein E gene (APOE) polymorphism is an important determinant for the development of various cardiovascular and neurodegenerative disorders. There have been conflicting reports of association of APOE polymorphism with dementia in Parkinson disease (PD). OBJECTIVE: To determine the relationship between APOE polymorphisms and plasma cholesterol concentration, and PD with dementia (PDD). DESIGN: Four-year (1999-2002) case-control study. SETTING: Academic medical center with inpatient and outpatient movement disorders services. Patients Consecutive white patients of the same ethnic background with PD. INTERVENTIONS: Strict clinical, neuropsychological, and neuroimaging criteria were used to exclude dementia with Lewy bodies, Alzheimer disease, and vascular dementia. Findings were compared in 2 clinical groups, including 98 patients (47 men and 51 women; mean age, 71 years) with PDD and 100 patients (52 men and 48 women; mean age, 62 years) with PD without dementia. MAIN OUTCOME MEASURES: Analysis of APOE genotypes and allelic frequency (polymerase chain reaction) and plasma cholesterol concentration (enzymatic assay) were evaluated by a clinician blinded to the clinical diagnosis, and findings were compared between the groups with PDD or PD without dementia. Multiple stepwise regression analysis and the Spearman rank correlation coefficient were used to evaluate relationships between dementia and both APOE polymorphism and cholesterol concentration. Statistical significance was set at P<.05. RESULTS: Epsilon4 allele frequencies were similar in PDD and PD without dementia (16.8% vs 19%, respectively). Cholesterol concentration, APOE genotypes, and allelic frequencies did not relate to PDD. CONCLUSIONS: In contrast to Alzheimer disease, when PDD is carefully defined, it is clearly not associated with APOE polymorphisms or with a distinctive plasma cholesterol profile. Ongoing longitudinal follow-up with emphasis on autopsy recruitment will enable further analyses of biochemical alterations underlying PDD.     

Apolipoprotein E allele frequencies in patients with late-onset sporadic Alzheimer's dementia in Hungary

Introduction – The presence of the apolipoprotein E4 allele (apoE4) has been recognized as a risk factor for the development of presenile and senile forms of Alzheimer's dementia (AD). Material and methods – The apoE alleles frequency of 71 normal controls (NC), 60 demented controls (DC) and 50 senile type AD subjects was determined by polymerase chain reaction in order to get data about the apoE polymorphism of the Hungarian AD population. Results – The apoE3/3 genotype was the most common in all groups. The apoE4 frequency was significantly higher (28%) in the AD group than that was (7% and 9%) in the NC and DC populations, respectively. No apoE4 homozygotes were found in the DC group and the number of heterozygotes was lower in the DC than in the AD group. Conclusion – The results are in good agreement with others in the literature and support the occurrence of an increased apoE4 allele frequency in Hungarian senile AD population.     

Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia

Background/Aims:

The aim of the following study is to compare the behavioral and psychological symptoms of dementia (BPSD) in patients of Alzheimer disease (AD) and vascular dementia (VaD).

Materials and Methods:

We used National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer''s Disease and Related Disorders Association criteria for diagnosing AD and National Institute of Neurological Disorders and Stroke-Association International pour la Recherche et l’Enseignement en Neurosciences Criteria for diagnosing VaD. VaD cohort was further subcategorized into small vessel and large vessel disease. The severity of cognitive impairment and the BPSD were studied by means of the Clinical Dementia Rating Scale (CDR) and the Neuropsychiatric Inventory respectively.

Results:

We studied 50 AD and 50 VaD patients of whom 38 were small vessels and 12 were large vessels VaD. The severity of dementia was comparable in both groups. The agitation/aggression, depression/dysphoria, anxiety, apathy/indifference, irritability, aberrant motor behavior, appetite and eating behavior and night-time behaviors occurred significantly more frequently in patients with VaD than AD. We found a weak positive correlation between the CDR score and the number of neuropsychiatric symptoms per patient in both cohorts. Elation/euphoria, agitation/aggression was significantly more frequent in patients with large vessel in comparison to small vessel VaD.

Conclusions:

BPSD are common in both types of dementia and they are more severe in VaD than AD when the groups have similar levels of cognitive impairment.