Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Consistent with previous reports, we observed a significant association of the APOE epsilon 4 allele with Alzheimer's Disease (AD) in a series of 91 autopsy-confirmed cases. The epsilon 4 allele frequency was higher in cases with a family history of AD-like dementia (0.54 +/- 0.07), although the epsilon 4 allele frequency in the AD cases with a negative family history (0.38 +/- 0.05) remained significantly greater than that for the non-AD control group (0.13 +/- 0.03). A similar increase in epsilon 4 allele frequency (0.54 +/- 0.07) was observed in the AD cases with amyloid angiopathy, compared to those who did not have amyloid angiopathy (0.36 +/- 0.04). Contrary to previous reports, no effect of the dosage of the epsilon 4 allele was found on the age of onset of dementia among the AD cases and, contrary to reports suggesting an association of epsilon 4 and atherosclerosis, the epsilon 4 allele frequency was similar in cases with or without concurrent brain infarcts. Modest but consistent correlations were observed between the dosage of epsilon 4 alleles and the cortical density of senile plaques, but not neurofibrillary tangles. The last finding suggests that the pathogenic events mediated by the epsilon 4 allele may be more directly involved in the formation of senile plaques, the identifying lesions in AD, than neurofibrillary tangles. A robust association of both the presence of an epsilon 4 allele and a family history of AD-like dementia with concurrent amyloid angiopathy occurred within our sample of AD cases. This association arose from an interaction of the epsilon 4 allele with a separate familial factor for which a family history of dementia served as a surrogate. These results suggest that amyloid angiopathy may be a common or central feature of a form of familial AD that is associated with the transmission of the APOE epsilon 4 allele.
 ...
PMID:Association of the apolipoprotein E epsilon 4 allele with clinical subtypes of autopsy-confirmed Alzheimer's disease. 781 May 77

The presence of apolipoprotein E-epsilon4 (APOE-epsilon4) allele has been implicated as a risk factor for Alzheimer's disease (AD). We examined the frequencies of APOE-epsilon4 alleles in age-matched controls and subgroups of 190 AD subjects exhibited cerebral amyloid angiopathy (CAA) and other frequently associated lesions. CAA was evident in 96% of the AD subjects, which were divided into two groups, one bearing mild or no apparent CAA and the other with moderate to severe CAA. APOE-epsilon4 allele frequency (48%) in the latter advanced CAA group was six times higher than in those who exhibited mild CAA. In the advanced CAA subjects, the occurrence of an epsilon4 allele was increased by a factor of 17 (95% confidence interval, 7.56 to 38.9). This was despite the fact that neocortical amyloid-beta plaque densities in the two groups were similar and that all of the AD subjects had met the accepted neuropathological criteria. We also observed that the degree of CAA severity was greatest in the group of subjects with the epsilon4/epsilon4 genotype. The association between CAA and APOE-epsilon4 was further implicated in two non-AD subjects among neurological controls with severe CAA. These two subjects, both homozygous for the APOE-epsilon4 allele, were primarily diagnosed as having Creutzfeldt-Jakob disease and Pick's disease in the absence of significant neocortical amyloid deposition. Allele frequency comparisons between neurological control subjects with CAA and those without likewise accorded a strong relationship between the APOE-epsilon4 allele and the presence of CAA. More remarkably, the epsilon4 allele frequency was highly associated with AD subjects exhibiting lobar or intracerebral hemorrhage, all of whom had advanced CAA. We observed that 36% of the AD subjects had concomitant cerebrovascular pathology resulting from single infarcts, multiple microinfarcts, ischemic white matter lesions, or petechial hemorrhages. Although the difference in APOE genotype distribution between subjects with and without cerebrovascular lesions did not reach statistical significance, we did note that the frequency of the epsilon4 allele was significantly higher in subjects with such pathology as compared with those without. However, we found no evidence to suggest that the acquisition of an APOE-epsilon4 allele or one of the alleles, epsilon2 or epsilon3, was a factor in the occurrence of atherosclerosis localized in the basal surface arteries. Analyses of our sample also confirm that there was a lower frequency of the APOE-epsilon2 allele in AD subjects and that the frequency of the epsilon4 allele in AD subjects with concomitant diffuse Lewy body disease was intermediate between controls and AD subjects. Our results suggest that the APOE-epsilon4 allele is a significant factor in the development of CAA in AD and reveal the possibility that APOE is an independent factor in CAA and other vascular abnormalities associated with AD.
 ...
PMID:Apolipoprotein E-epsilon4 alleles in cerebral amyloid angiopathy and cerebrovascular pathology associated with Alzheimer's disease. 866 92

To determine whether apolipoprotein E epsilon 2 (APOE-epsilon 2) affects neuropathology in aging and Alzheimer's disease (AD), we compared beta-amyloid plaque (A beta P) and neurofibrillary tangle densities, neuropil thread formation, and amyloid angiopathy in five APOE-epsilon 2/3 AD patients, five APOE-epsilon 3/3 AD patients, five APOE-epsilon control patients, and five APOE-epsilon 3/3 control patients. We examined the (frontal and parietal) neocortex, hippocampus, entorhinal cortex, and cerebellum and found A beta P densities to be lower (t = 3.121, p = 0.011) in the cortex of APOE-epsilon 2/3 AD patients than in APOE-epsilon 3/3 AD patients. Amyloid angiopathy was also less in APOE-epsilon 2/3 patients than in APOE-3/3 patients (U = 4.500, p = 0.027). Control APOE-epsilon 2/3 brains had little AD-related pathology; even our 102-year-old control case showed few A beta Ps compared with the elderly APOE-epsilon 3/3 cases. The APOE-epsilon 2/3 genotype may influence pathologic phenotype in some aged normal and AD populations.
 ...
PMID:Apolipoprotein E-epsilon 2 and Alzheimer's disease: genotype influences pathologic phenotype. 904 Jul 48

Stroke patients are more likely to develop dementia than age- and sex-matched controls but the pathogenesis of dementia remains unresolved in most of them. The aim of this review is to determine, from the available literature, the theoretical reasons for a stroke patient to become demented. We found three distinct factors that may explain the occurrence of dementia after a stroke. Firstly, post-stroke dementia may be the direct consequence of the vascular lesions of the brain: this is the most likely cause in patients with normal cognitive functions before a strategic infarct, especially in young patients, in Icelandic-type hereditary amyloid angiopathy and in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. Secondly, post-stroke dementia may be due to an associated asymptomatic Alzheimer pathology; the reasons for such an association are that (1) some cases of dementia occurring after a stroke are progressive and Alzheimer's disease (AD) is the most frequent cause of progressive dementia; (2) age and APOE epsilon 4 genotype are risk factors for both AD and ischaemic stroke; (3) a vasculopathy is often associated with AD. Lastly, white matter changes may also contribute to dementia because they often indicate small-vessel disease and a higher risk of stroke recurrence, and may lead to slight cognitive impairment. Finally, the summation of vascular lesions of the brain, white matter changes, and Alzheimer pathology might lead to dementia, even when each type of lesion, on its own, is not severe enough to induce dementia. Therefore, in patients followed up after a stroke, the term "post-stroke dementia" is probably more appropriate than that of vascular dementia because it includes all possible causal factors.
 ...
PMID:Why are stroke patients prone to develop dementia? 905 Sep 53

Abeta peptides are thought to be centrally involved in Alzheimer's disease (AD) pathogenesis, although Abeta's pathophysiological mechanisms remain to be elucidated. We previously showed that soluble beta-amyloid1-40 (Abeta) and Abeta1-42 exhibit vasoactive properties, and are able to promote vasoconstriction in rat aortae induced by an endogenous vasoconstrictor, endothelin-1. It is well established that the APOE epsilon4 allele confers risk for both familial and sporadic AD, as well as for hypertension. We now report that physiologic amounts (10 nM) of specific human recombinant apoE isoforms are vasoactive (E4 > E3, and not E2) in isolated rat aortae. In order to investigate if various apoE isoforms could modulate Abeta vasoactivity, we co-incubated Abeta1-40 with various isoforms of apoE in our tissue bath system. Our results show that, while none of the APOE isoforms are able to affect the maximum constriction induced by Abeta; the apoE E4 isoform synergistically enhances the rate of vasoconstriction induced by Abeta. Our data suggest that apoE may promote hypertension and contribute to AD pathogenesis via enhancement of vasoconstriction, and support a link between hypertension, cerebral amyloid angiopathy and AD.
 ...
PMID:Isoform-specific vasoconstriction induced by apolipoprotein E and modulation of this effect by Alzheimer's beta-amyloid peptide. 985 6

There is increasing evidence that risk factors for vascular disease and stroke are associated with cognitive impairment and Alzheimer's disease. This paper reviews current knowledge on the relationship between risk factors for stroke and Alzheimer's disease. The focus will be on 'classical' risk factors, including age and gender, socioeconomic status, diabetes, cholesterol, prior cardiovascular disease, atrial fibrillation, cigarette smoking and alcohol use; as well as on factors that more recently have been recognized as putative risk factors, including APOE genotype, serum homocysteine concentration, relative abnormalities in the hemostatic and thrombotic systems, and inflammation.
 ...
PMID:Risk factors for vascular disease and dementia. 1042 64

Twelve patients who had surgical removal of a cerebral haematoma had a biopsy or autopsy diagnosis of cerebral amyloid angiopathy-related haemorrhage (CAAH). Ten had a cortical biopsy at the time of surgery and eight reports of these were interpreted as showing CAA to be the cause of the haemorrhage. The diagnosis in the remaining two was made at autopsy. Six patients had a biopsy and autopsy, resulting in a 67% (four of six) biopsy sensitivity. Amyloid beta-protein (A beta) immunohistochemistry was more sensitive than tinctorial stains in detecting CAA. As previously reported in CAAH there was an excess of patients with the APOE epsilon 2 allele (33% versus 16% in a control group). Four patients (33%) were alive at 3 months. Despite surgical intervention, CAAH has a poor outcome in patients with impaired consciousness. Clinical awareness of CAAH and use of A beta immunostaining may increase the diagnostic yield from cerebral biopsy.
 ...
PMID:Surgical intervention, biopsy and APOE genotype in cerebral amyloid angiopathy-related haemorrhage. 1062 76

The epsilon 4 allele of apolipoprotein E (APOE denotes gene; apoE denotes protein) is a major risk factor for Alzheimer's disease (AD). More recent evidence indicates an association with a poor outcome after acute brain injury including that due to head trauma and intracerebral hemorrhage. APOE gene polymorphism also influences the risk of hemorrhage in cerebral amyloid angiopathy. These diverse brain disorders seem to have some mechanisms in common. The multiplicity of the roles of apoE within the central nervous system is currently being unraveled. For example, apoE can interact with amyloid beta-protein and tau, proteins central to the pathogenesis of AD. In addition to these effects, it is proposed that one of the major functions of apoE is to mediate neuronal protection, repair and remodeling. In all of the different roles proposed, there are marked apoE-isoform specific differences. Although it remains to be clarified which is the most important mechanism(s) in each disorder in which apoE is involved, these isoform specific differences seem to underly a genetically determined susceptibility to outcome from acute brain injury and to AD with APOE epsilon 4 conferring relative vulnerability. This review focuses on apoE research, from clinical studies to animal models, in AD, acute brain injury and cerebrovascular disease and explores the common mechanisms that may explain some of the complex underlying neurobiology.
 ...
PMID:The role of apolipoprotein E in Alzheimer's disease, acute brain injury and cerebrovascular disease: evidence of common mechanisms and utility of animal models. 1086 9

To verify the association between APOE4 frequency and various dementias in Taiwan Chinese individuals, APOE genotypes were determined in patients with dementia of Alzheimer's type (AD), vascular dementia (VD), dementias due to other general medical conditions (OD), and dementia of Alzheimer's type with cerebral vascular disease (mixed type dementia; MD). Only AD patients exhibited higher APOE4 frequency (OR = 2.95, p = 0.001) than controls after Bonferroni correction to control the overall type I error rate for the multiple testing. No such difference was observed among VD, OD, MD and control groups. The lack of association between VD and APOE4 allele frequency suggests that APOE4 allele does not associate with cerebrovascular pathology related dementia in Taiwan Chinese.
 ...
PMID:Apolipoprotein E polymorphism in various dementias in Taiwan Chinese population. 1245 37

The relative amounts of amyloid beta-protein (A beta) in cerebral blood vessels and parenchyma vary considerably amongst patients with Alzheimer's disease (AD). Although several mechanisms have been proposed to explain this variability, the underlying genetic and environmental determinants are still unclear, as are the functional consequences. Polymorphisms in APOE, the gene for apolipoprotein E (ApoE), influence the risk of developing AD and of deposition of A beta within the brain. We examined the relationship between the APOE genotype and the relative extent of accumulation of A beta as plaques within the cerebral parenchyma and in cortical blood vessels in the form of cerebral amyloid angiopathy (CAA), in autopsy brain tissue from 125 AD cases and from 53 elderly, neurologically normal controls of which 19 had CAA without other neuropathological features of AD. In the AD cases, we also assessed whether the severity of CAA was related to the age of onset and duration of dementia, risk factors for atherosclerotic vascular disease, and histologically demonstrable cerebral infarcts or foci of haemorrhage. The APOE genotype was determined by a standard polymerase chain reaction-based method. Paraffin sections of frontal, temporal and parietal lobes were immunolabelled for A beta and the parenchymal A beta load (total A beta minus vessel-associated A beta) was quantified by computer-assisted image analysis. CAA severity was scored for cortical and leptomeningeal vessels. The relevant clinical data were obtained from the database of the South West Brain Bank. In AD, we found the severity of CAA to be strongly associated with the number of epsilon 4 alleles (P < 0.0001) but the parenchymal A beta load to be independent of APOE genotype. Cases with severe CAA had a lower parenchymal A beta load than had those with moderate CAA (P = 0.003). Neither the severity of CAA nor the parenchymal A beta load correlated with age of onset, duration of disease or age at death, and the severity of CAA also did not correlate with the presence of cerebral infarcts or foci of haemorrhage. These findings indicate that possession of the APOE epsilon 4 allele favours vascular over parenchymal accumulation of A beta in AD. This may influence the pathogenesis of neurodegeneration in epsilon 4-associated AD.
 ...
PMID:APOE epsilon 4 influences the pathological phenotype of Alzheimer's disease by favouring cerebrovascular over parenchymal accumulation of A beta protein. 1278 20


1 2 3 4 5 6 7 8 Next >>