Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A quick and practical procedure based upon the principles of affinity chromatography has been developed and specifically adopted for the separation of serum lipoproteins into their respective alpha- and beta-lipoprotein fractions. The cholesterol, phospholipids, apoproteins, and triglycerides of these two lipoprotein fractions--the high-density lipoproteins (HDL) and lower density lipoproteins--can be directly measured independently after this separation. The sums of each fraction agree with total serum components when independently assayed. The affinity column is packed with heparin bound in high capacity to agarose. The beta-lipoproteins (low-density and very-low-density lipoproteins) and HDL-containing apolipoprotein E are absorbed to the column support; the alpha-lipoproteins (non-apolipoprotein E) pass through. The beta-lipoproteins are subsequently desorbed from the column support with saline. The direct assay of both the "protective" alpha-lipoprotein cholesterol (HDL cholesterol) and of the presumably atherogenic lower-density beta-lipoprotein cholesterol (LDL + VLDL cholesterol) permits calculation of a beta-: alpha-lipoprotein cholesterol ratio, which may better indicate a patient's risk of stroke or coronary heart disease than does the value for HDL cholesterol alone.
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PMID:Direct determination of lipoprotein cholesterol distribution with micro-scale affinity chromatography columns. 708 54

Controversies exist concerning the role of hypercholesterolaemia as a risk factor for nonhaemorrhagic stroke because intracranial arteries seem to be more resistant than coronary arteries to cholesterol-induced endothelial damage. Only very high levels of serum cholesterol seem to be a significant risk factor. It is possible that coronary heart disease may occur earlier in life than cerebrovascular atherosclerosis, and it could then become the cause of stroke. In our view, the causal relationship between very low levels of serum cholesterol and haemorrhagic stroke is unlikely, and cholesterol-lowering treatment appears to be safe. New studies should consider the particular metabolic aspects of intracranial arteries and the independent role of lipoprotein (a), apolipoprotein E phenotypes and other molecular and genetic mechanisms involved in atherosclerotic cerebrovascular disease.
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PMID:Hyperlipidaemia and atherosclerotic cerebrovascular disease. 767 Jul 53

The allele e4 (apo e4) of apolipoprotein E (apo E) has been associated with an increased risk for coronary heart disease (CHD) in cross-sectional studies in middle-aged subjects. We investigated the risk of CHD and stroke with respect to the number of apo e4 alleles in a prospective study of a Finnish nondiabetic cohort including 1067 subjects 65 to 74 years old at baseline. During the 3.5-year follow-up, CHD mortality was 2.8%, total CHD incidence 6.9%, and the cumulative occurrence of CHD (prevalence at baseline and the 3.5-year incidence combined) 17.0%. The incidence of stroke was 3.4%, and the cumulative occurrence of stroke was 6.0%. The CHD mortality was 3.4% in subjects with no apo e4 allele (n = 734), 1.7% in those with one apo e4 allele (n = 296), and 0% in subjects with two apo e4 alleles (n = 37) (P = NS between the three groups). The incidence of CHD according to the number of apo e4 alleles was 6.9% (no apo e4 alleles), 7.4% (one apo e4 allele), and 2.7% (two apo e4 alleles), and the cumulative occurrence of CHD was 16.5%, 18.6%, and 13.5%, respectively (P = NS). The incidence of stroke was 3.8% in subjects with no apo e4 allele, 2.7% in those with one apo e4 allele, and 0% in those with two apo e4 alleles (P = NS). The cumulative occurrence of stroke was 6.0%, 6.4%, and 2.7%, respectively (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Apolipoprotein E4 phenotype is not an important risk factor for coronary heart disease or stroke in elderly subjects. 767 Sep 39

Alzheimer's disease (AD) is rapidly moving from the obscure category of degenerative diseases to the more precise one of metabolic disorders. Recent discoveries have substantiated the hypothesis that AD results from the deposition of beta-amyloid, which is formed by polymers of a proteolytic fragment of the amyloid protein precursor (APP), and may induce intraneuronal aggregation of the microtubule-associated protein tau into paired helical filaments and neuronal death. There is also evidence that AD is a heterogeneous age-related disorder of multifactorial origin, which may arise as a consequence of point mutations of genes encoding APP or other proteins involved in its metabolism (familial AD), or a combination of genetic and non-genetic factors (sporadic AD). Familial AD displays genetic and phenotypic heterogeneity, meaning that mutations of different genes may cause the AD phenotype, and that different mutations of the same gene may cause phenotypically distinct disorders, including Alzheimer-type dementia and cerebral amyloid angiopathy with cerebral hemorrhages and stroke. On the other hand, aging, gender, head trauma, and variants of the apolipoprotein E gene have been shown to increase the risk of developing the more prevalent sporadic form of AD. The mechanisms by which these factors influence amyloidogenesis are beginning to be understood, and this will provide a rational basis for future therapy. Knowledge of the molecular basis of AD would eventually allow accurate risk prediction before the disease becomes clinically apparent, and better chances for early treatment and prevention.
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PMID:Alzheimer's disease, beta-amyloidosis, and aging. 769 97

Advances in the study of cerebrovascular disease suggest that many risk factors for stroke are under genetic influence. Epidemiologic studies show that parental and sibling histories of cerebral ischemic events are associated with an increased risk of stroke. Explanations for familial stroke aggregation include differential phenotypic expression of apolipoprotein (a) and apolipoprotein E, racial variations in the distribution of vascular disease, identification of the autosomal-dominant disorder cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy, specific point mutations in the mitochondrial-related disorders, and identification of the clinical significance of hereditable coagulopathies. Greater understanding of these factors may lead to early recognition of and intervention in stroke.
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PMID:Genetics of ischemic stroke. 774 12

The apolipoprotein E gene (Apo E) type 4 allele is a genetic risk factor influencing the development and age of onset of Alzheimer's disease. Because Parkinson's disease shares many characteristics of Alzheimer's disease, we studied the frequencies of Apo E genotypes in a cohort of 52 Parkinson's disease patients with dementia and 61 patients without dementia. Dementia was determined per National Institute of Neurological and Communicative Disorders and Stroke criteria and Mattis Dementia Rating Scale (DRS) < 126. Normal cognition was defined as DRS > 132. Apo E genotype and allele frequencies did not differ between demented and nondemented parkinsonian patients. Neither group's genotype and allele frequencies differed from that of a nondemented population of 78 controls. We conclude that the Apo E epsilon 4 allele influences neither the development of Parkinson's disease nor the dementia associated with Parkinson's disease.
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PMID:Apolipoprotein E genotypes in Parkinson's disease with and without dementia. 784 65

Age-dependent neurodegeneration in Alzheimer disease (AD) may be viewed as a complex interaction among: (i) susceptibility polymorphisms, (ii) somatic mutations or alterations that occur over extended periods of time, and (iii) environmental interactions. Putative "sporadic" diseases appear to have a much stronger genetic component than had been considered previously. For example, in Alzheimer disease, apolipoprotein E is a major susceptibility locus that accounts for approximately half the heritability. Specific APOE genotypes are associated with different relative risks and age of onset distributions. Disease may be expressed as a confluence of several genetic risk factors, superimposed upon the age-dependent increments of somatic mitochondrial mutations, and environmental determinants such as head injury, stroke, or hypoxia. A matrix involving each of these complex factors may influence the age of onset of AD in a particular individual. With careful clinically based family and epidemiological studies, it is now possible to tease out the relevant genetic contributions from the confluence of other factors leading to complex disease affecting specific sets of neurons. The highly intricate maze of contributing factors provides many potential unanticipated opportunities to design rational therapeutic and preventative strategies.
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PMID:Apolipoprotein E, a gene with complex biological interactions in the aging brain. 936 Dec 94

The relationship between the apolipoprotein E (apoE) and beta-fibrinogen G/A-455 polymorphisms and cerebrovascular disease (CVD) was examined in the present study. We compared 227 patients with the subtypes of CVD (large-vessel disease, lacunar stroke, cardiac embolism, or undetermined pathomechanisms) with 225 control subjects. The occurrence of apoE isoforms (E2, E3, and E4) and the beta-fibrinogen G/A-455 genotype was determined in these individuals. No differences in apoE polymorphisms or allele frequencies between the CVD patients and control subjects were found. However, analysis of apoE genotypes as a function of stroke subtype revealed that the apoE4 allele was significantly more common in those patients with macroangiopathy-associated CVD. The only CVD risk factor that distinguished patients with the E4 allele from those with other apoE genotypes was elevated cholesterol. No association between the beta-fibrinogen G/A-455 polymorphism and CVD was found. However, homozygosity for the A allele was more common in patients with CVD resulting from large-vessel disease. These data demonstrate that the apoE4 allele and the AA genotype of the beta-fibrinogen G/A-455 polymorphism occur significantly more frequently in patients with CVD resulting from stenosis of large, brain-supplying vessels. Such genetic analyses may further our understanding of the etiology of cerebrovascular disease.
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PMID:The apolipoprotein E and beta-fibrinogen G/A-455 gene polymorphisms are associated with ischemic stroke involving large-vessel disease. 940 70

The aim of this review is to determine the influence of coincidental cerebrovascular pathology on the symptomatology and course of Alzheimer's disease (AD). The link between stroke and AD is probably higher than expected by chance for the following reasons: (i) both pathologies share genetic risk factors such as the epsilon 4 allele of the apolipoprotein E gene; (ii) AD patients have changes in the brain vessels that may lead to either ischemic or hemorrhagic stroke or white matter changes or both; (iii) there is evidence of an increased risk of stroke in AD patients; (iv) there is evidence of a frequent association of AD and stroke at autopsy. Because of the summation of the various types of lesions, stroke lesions may lead to an increase progression of cognitive decline in AD patients. Recognition of a vascular component in a dementia syndrome is therefore useful for the management of AD patients. Whether an optimal management of risk factors for stroke may delay the clinical expression of dementia in patients with preclinical Alzheimer pathology should be evaluated.
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PMID:The influence of coincidental vascular pathology on symptomatology and course of Alzheimer's disease. 985 Sep 20

Alzheimer's disease (AD) patients with moderate dementia show losses in olfactory threshold, odor identification and odor memory. Sensitivity and specificity of olfactory testing is significant, with the greatest power of accurate diagnosis in the more cognitively loaded olfactory tasks. In patients with very mild AD or in patients at risk for the disease because of their mild cognitive impairment, losses are apparent for odor identification, odor recognition memory and odor threshold, with the best sensitivity in the identification task. Persons who are either heterozygous or homozygous for the epsilon 4 allele of apolipoprotein E (ApoE) have an increased risk of Alzheimer's disease, although they show no dementia in the preclinical period. Evidence of olfactory dysfunction in this population might be reflective of an incipient dementing process. We have recently examined olfactory function in a group of normal elderly persons who have undergone genetic testing for the Apoe4 allele. These individuals consisted of all normal control subjects at the University of California, San Diego (UCSD) Alzheimer's Disease Research Center (ADRC) who had undergone both the genetic testing and testing for olfactory function. All had been diagnosed as normal control participants by two different neurologists who applied the National Institute of Neurological Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINDS-ADRDA) criteria for dementia. Persons with a history of alcoholism, drug abuse, learning disability or neurologic or psychiatric illness (including depression) were excluded. In this population, persons with the Apoe4 allele showed significantly poorer odor identification than those without an epsilon 4 allele. Early appearance of olfactory deficits in the progression to AD in persons with the epsilon 4 allele suggests diagnostic utility in olfactory testing.
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PMID:Apolipoprotein E status is associated with odor identification deficits in nondemented older persons. 992 80


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