Apolipoprotein E epsilon 4 allele distribution in alcoholic dementia and in Alzheimer's disease in Japan

The apolipoprotein E epsilon 4 allele has been associated with both familial and sporadic Alzheimer's disease (AD). Given its possible role in nerve repair and growth, it is plausible that apolipoprotein E may be a common denominator in the pathogenesis of several dementing diseases. Therefore, we investigated epsilon 4 frequencies in demented and nondemented alcoholics, as well as in patients with sporadic AD and controls in Japan. No significant differences in allele frequencies was found between demented and nondemented alcoholics and controls, while a significant association was demonstrated between AD and the epsilon 4 allele. These results support a specific role of epsilon 4 in the pathogenesis of AD, rather than a more general role for epsilon 4 in dementing illnesses.     

Apolipoprotein E epsilon4 allele frequency is increased in Parkinson''s disease only with co-existing Alzheimer pathology

Coronary perforation can be managed with prolonged balloon inflations, covered stents, or embolization of the vessel. We report on a case of a balloon-induced perforation of the distal left anterior descending artery, that was sealed by injecting preclotted autologous blood through the balloon catheter lumen at the site of the perforation. The patency of the distal vessel was maintained.     

Apolipoprotein E type 4 allele and cerebral glucose metabolism in relatives at risk for familial Alzheimer disease

OBJECTIVE: Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD. DESIGN: After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups. SETTING: University medical center. PATIENTS: At risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE epsilon 4 did not differ from those without APOE epsilon 4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3). MAIN OUTCOME MEASURES: Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18. RESULTS: Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 compared with those without APOE epsilon 4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4. CONCLUSIONS: These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabolism and increased asymmetry in non-demented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.     

ApoE allele frequencies in Italian sporadic and familial Alzheimer's disease

Recent studies have provided evidence of association of apolipoprotein E (ApoE) epsilon 4 allele and late onset familial and sporadic Alzheimer's disease (AD). Epidemiological studies have established allelic variation at the ApoE locus. We have analyzed the ApoE gene polymorphism in a sample of 446 Italian subjects. Our data confirm a significant association between epsilon 4 allele and sporadic AD. The frequency of epsilon 4 allele in early onset familial AD patients was comparable to control values suggesting that epsilon 4 allele does not represent a risk factor for early onset familial AD (EOFAD). Moreover, we found a not previously reported association between ApoE epsilon 2 allele and sporadic AD and EOFAD.     

Apolipoprotein E epsilon 2 allele and risk of stroke in the older population

BACKGROUND AND PURPOSE: There is evidence for a role of apolipoprotein E (apoE) in atherosclerosis. Coronary heart disease morbidity is higher in persons carrying an epsilon 4 allele and lower in those carrying an epsilon 2 allele, but the effect on cerebrovascular disease is controversial. We estimated the risk of stroke associated with different apoE genotypes in older persons. METHODS: At the sixth annual follow-up of the Iowa cohort of the Established Populations for Epidemiologic Studies of the Elderly, 1664 persons aged > or = 71 years and free of stroke were genotyped for apo E. Occurrence of ischemic strokes was prospectively assessed from subsequent hospital discharge records and death certificates. RESULTS: One hundred fifty persons had an ischemic stroke over the subsequent 5 years (21.2 per 1000 person-years). The presence of epsilon 3 and epsilon 4 did not influence stroke risk. Among persons aged < 80 years at the time of genotyping, epsilon 2 carriers had lower risk of incident stroke, while no effect was detected in the older group. Compared with epsilon 2 carriers aged 70 to 79 years (reference group), those in the same age group and not carrying an epsilon 2 had 2.6-fold higher risk of incident stroke, and those aged > or = 80 years had even higher risk of stroke but without any difference according to presence/absence of epsilon 2 (relative risks 3.6 and 3.3). Results remained substantially unchanged when adjusted for potential confounders and in models estimating the effect of apoE polymorphism on the risk of developing a stroke at ages between 70 and 79 years (56 events) and separately at ages > or = 80 years (94 events). CONCLUSIONS: The conditioning influence of age on the protection conferred by the apoE epsilon 2 allele on stroke risk may account for previous controversies. This hypothesis should be verified in a population with a wider age range.     

Apolipoprotein E epsilon 4 allele distribution in Wernicke-Korsakoff syndrome with or without global intellectual deficits

Recent genetic studies show that the apolipoprotein E (ApoE) epsilon 4 allele is a risk factor for Alzheimer's disease (AD). Whether this allele is associated with other dementing diseases is the next important question. The information could provide a clue to the pathogenetic role of ApoE. In the present study, patients with Wernicke-Korsakoff syndrome (WKS) of alcoholic etiology were divided into two groups according to the severity of intellectual deficits, i.e., those of "classical" Korsakoff patients with preserved intellectual function other than amnesia and those with global intellectual deficits. Genotyping showed that the frequency of ApoE epsilon 4 allele was significantly higher in the patients with global deficits, suggesting the involvement of this allele in the intellectual decline of WKS. In contrast, distributions of other two markers, alpha 1-antichymotrypsin and presenilin-1, did not differ between the two groups. These results added further support to the notion that the consequence of acute insult to the brain is influenced by the ApoE genotype, and suggested ApoE's role in the development of a certain group of "alcoholic dementia."     

Ethnic differences in interferon-alpha allele frequencies

We analyzed microsatellite instability (MSI) and loss of heterozygosity (LOH) at 17 microsatellite markers located on chromosomes 2p, 3p, 5q, 6q, 9p, 9q, 17p and 18q in 19 randomly selected keratoacantomas (KAS), in one cutaneous lesion that histologically could not unequivocally be differentiated from squamous cell carcinoma, and in one patient with multiple KAs of longstanding duration. The goals of our study were to determine whether, in a similar manner to some visceral carcinomas, genomic instability could be detected in KAs and to clarify whether molecular analysis might be useful to further characterize KA. MSI was observed in 2 of 21 cases (9.5%) at 5 of 17 loci examined. In one patient with a solitary KA, the presence of MSI and a family history of visceral malignant tumours suggested that the patient might have belonged to a family with Muir-Torre syndrome. In one other MSI+ KA, a definite differential diagnosis in relation to squamous cell carcinoma could not be established. In addition, one sample displayed LOH at 2 of 17 loci analysed whereas in the patient with multiple KAs, LOH at one locus was the only alteration found. In conclusion, the low frequency of MSI and LOH detected in our study suggests that these genetic events are uncommon in KA unless it is associated with a familial disease (e.g. Muir-Torre syndrome) or it has more aggressive histological features.     

Apolipoprotein E in the brain and its role in Alzheimer's disease

Recent evidence indicates that apolipoprotein E (apoE) plays a central role in the brain response to injury. The coordinated expression of apoE and its main receptor, the apoE/apoB (LDL) receptor, appears to regulate the transport of cholesterol and phospholipids during the different phases of the reinnervation process. The recent discovery that a peculiar form of apoE, the apoE4, is strongly linked to both sporadic and familial late onset Alzheimer's disease (AD) raises the possibility that a dysfunction of the lipid transport system associated with compensatory sprouting and synaptic remodelling could be central to the AD process. The role of apoE in the central nervous system (CNS) is particularly important in relation to the function of the cholinergic system which relies to a certain extent on the integrity of phospholipid homeostasis in neurons. Recent evidence suggests that apoE4 allele has a direct impact on cholinergic function in AD.     

Apolipoprotein E epsilon4 allele as a genetic risk factor for left ventricular failure in homozygous beta-thalassemia

In homozygous beta-thalassemia, the organ damage is mainly attributed to excessive iron deposition through the formation of oxygen free radicals. Despite appropriate transfusion and chelation therapy and low ferritin levels, patients still develop organ failure, heart failure being the main cause of death. This study was designed to determine whether the decreased antioxidant activity of the apolipoprotein E (APOE) 4 allele could represent a genetic risk factor for the development of left ventricular failure (LVF) in beta-thalassemia homozygotes. A total of 251 Greek beta-thalassemia homozygotes were studied. Patients were divided in three groups: group A (n = 151) with no cardiac impairment, group C (n = 47) with LVF, and 53 patients with LV dilatation and normal LV systolic function constituted the group B. DNA was obtained from all patients, and the polymerase chain reaction was used to analyze the polymorphism at the APOE locus. The APOE allele frequencies were compared with those of a Greek control sample of 216 healthy blood donors. Patients with no cardiac impairment had an APOE 4 allele frequency (7.9%) not different from population controls (6.5%, P > .05), while patients with LVF had a significantly higher frequency of APOE 4 (12.8%) than the controls (P < .05, odds ratio = 2.11, 95% confidence interval 1.03 to 4.32). The APOE 4 allele may represent an important genetic risk factor for the development of organ damage in homozygous beta-thalassemia.     

The apolipoprotein E epsilon4 allele and outcome in cerebrovascular disease

BACKGROUND AND PURPOSE: Polymorphism of the apolipoprotein E gene (APOE) may influence outcome after traumatic brain injury and intracerebral hemorrhage, with the epsilon4 allele being associated with poorer prognosis. We investigated APOE allele distribution in acute stroke and the effect of the epsilon4 allele on outcome. METHODS: APOE genotypes were determined in 714 stroke patients: 640 ischemic stroke and 74 intracerebral hemorrhage patients. The survival effect of the epsilon4 allele was assessed with the use of a stratified log-rank test. A Cox proportional hazards regression model was used to estimate the independent effect of epsilon4 dose (0, 1, or 2) on survival, and logistic regression was used to determine the effect on 3-month outcome (good if alive at home, poor if in care or dead). RESULTS: Allele distribution matched the general population with no difference between the ischemic and hemorrhagic groups. Survival in the entire cohort was unaffected by epsilon4 dose. Improved survival with increasing epsilon4 dose was found in the ischemic group (relative hazard=0.76 per allele; P=0.04). If transient ischemic attacks were excluded, a trend for improved survival persisted (P=0.06). With intracerebral hemorrhage, a trend was seen toward reduced survival with epsilon4 (P=0.07, log-rank test). Three-month outcome in the ischemic group was unaffected by epsilon4 dose, and a trend toward poorer outcome with epsilon4 was seen for intracerebral hemorrhage (P=0.10). CONCLUSIONS: The APOE epsilon4 allele had divergent effects on survival and outcome in ischemic and hemorrhagic strokes in this population. The reported adverse effect on patients with intracerebral hemorrhage was supported. The favorable survival effect on ischemic stroke patients requires further study.     

Ciliary neurotrophic factor null allele frequencies in schizophrenia, affective disorders, and Alzheimer''s disease

The membrane assembly of outer membrane proteins is more complex than that of transmembrane helical proteins owing to the intervention of many charged and polar residues in the membrane. Accordingly, the predictive accuracy of transmembrane beta strands is considerably lower than that of transmembrane alpha helices. In this paper we develop a set of conformational parameters for membrane spanning beta strands. We formulate an algorithm to predict the transmembrane beta strands in the family of bacterial porins based on the conformational parameters and surrounding hydrophobicities of amino acid residues. A Fortran program has been developed which takes the amino acid sequence as the input file and gives the predicted transmembrane beta strand as output. The present method predicts at an accuracy level of 82% for all the bacterial porins considered.     

Apolipoprotein e4 allele and cognitive decline in elderly men

OBJECTIVES: To determine whether polymorphism of apolipoprotein E--notably, the e4 allele--predicts cognitive deterioration in the general population. DESIGN: Population based cohort investigated in 1990 and in 1993. SETTING: Zutphen, the Netherlands. SUBJECTS: Representative cohort of 538 Dutch men aged 70-89 at baseline. MAIN OUTCOME MEASURES: Cognitive function assessed by mini mental state examination, change in cognitive function and incidence of impaired cognitive function at three years. RESULTS: The baseline prevalence of impaired cognitive function (mini mental state examination score < or = 25) was higher among carriers of the e4 allele compared with men without the allele (41.0% (55) v 31.1% (122) P = 0.03), and this result was still valid after adjustment for age, occupation, smoking, alcohol use, and cardiovascular diseases. The decline in cognitive function at three years was largest in men homozygous for e4 (-2.4 points), intermediate in those heterozygous for e4 (-0.7 points), and lowest in men without e4 (-0.1 points), and it was independent of other risk factors (P = 0.02). The risk of developing impaired cognitive function during follow up was significantly increased in allele carriers compared with non-carriers (27.6% (16/58) v 15.5% (32/207)). The adjusted odds ratio was 2.87 (95% confidence interval 1.29 to 6.42). Twenty two per cent of the risk of developing impaired cognitive function in this population may be attributable to the e4 allele. CONCLUSIONS: The apolipoprotein e4 allele predisposes to cognitive decline in a general population of elderly men.     

Apolipoprotein E polymorphism in elderly east Africans

Current advances have shown the apolipoprotein E (APOE)-epsilon 4 allele to be highly associated with late-onset familial and sporadic Alzheimer's disease (AD) in Western populations. The association of APOE allele frequencies and dementia remain unknown in populations from developing countries. We recently initiated a project to examine APOE frequencies in non-demented and demented elderly East Africans. Blood DNA collected from two hospital-based populations showed that the APOE allele frequencies in a group of non-demented 67 Tanzanians over the age of 65 years were found to be 14% for epsilon 2, 61% for epsilon 3 and 25% for epsilon 4. By comparison, the frequency of APOE-epsilon 4 in an age-matched demented group was also 25%. Assessment of APOE genotypes in the group of elderly Kenyan subjects from Nairobi also revealed high frequencies of the epsilon 4 allele with no clear difference in frequency between demented and non-demented subjects. Our preliminary observations suggest that elderly East Africans with no apparent clinical AD possess relatively high APOE-epsilon 4 allele frequencies compared to normal ageing subjects from Western countries including African-Americans. These results appear similar to those reported in a recent study in Nigerian Africans where a lack of correlation between APOE-epsilon 4 allele frequency and Alzheimer type of dementia was noted, and imply that APOE-epsilon 4 allele may not necessarily be a risk factor in some populations of Africa.     

D1S80 allele frequencies in a Chinese population

Allele frequencies for the VNTR locus D1S80 were determined in a Chinese population sample using the polymerase chain reaction and subsequent analysis of the amplified products by polyacrylamide gel electrophoresis and silver staining. A total of 18 nominal D1S80 alleles were observed in 105 unrelated Chinese. The data demonstrate that D1S80 is highly polymorphic in Chinese with a heterozygosity of 90.5%. The D1S80 frequency distribution meets Hardy-Weinberg expectations. This D1S80 data can be used in forensic analyses and paternity tests to estimate the frequency of a DNA profile in a Chinese population.     

Association of apolipoprotein E epsilon 4 allele with bulbar-onset motor neuron disease

BACKGROUND: Variants of the apolipoprotein E (APOE) gene influence the age of onset of Alzheimer's disease. APOE may influence the presentation of other neurological diseases. We investigated the relationship between the allelic variants of apolipoprotein E and clinical presentation in motor neuron disease. METHODS: 123 patients with motor neuron disease and 121 controls were studied. Diagnosis, location of onset and date of onset were recorded prospectively. Genotyping was performed blind to clinical information. FINDINGS: Possession of at least one epsilon 4 allele was significantly more common in patients with bulbar onset motor neuron disease (14/33, 42%) than in limb onset patients (20/90, 22%) and controls (26/121, 21%) (chi 2 = 4.93, p = 0.026 and chi 2 = 5.91, p = 0.015, respectively). INTERPRETATION: These results suggest that the apolipoprotein E epsilon 4 allele may influence the pattern of motor neuron loss in motor neuron disease and that it may affect neuronal function in ways unrelated to the deposition of beta-amyloid or accumulation of neurofibrillary tangles.     

HLA-B44 allele frequencies and haplotypic associations in three European populations

Thrombosis during pregnancy poses special problems. This review focuses on risk factors for the development of venous thromboembolism during pregnancy, diagnosis of deep vein thrombosis and pulmonary embolism during pregnancy, therapeutic recommendations for the treatment of acute thromboembolism during pregnancy, and thromboprophylaxis in the pregnant woman. Management of pregnant women with antiphospholipid antibodies is also reviewed.