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APOE*4 Allele

About: APOE*4 Allele is a(n) research topic. Over the lifetime, 68 publication(s) have been published within this topic receiving 11132 citation(s).

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Journal ArticleDOI: 10.1126/SCIENCE.8346443
13 Aug 1993-Science
Abstract: The apolipoprotein E type 4 allele (APOE-epsilon 4) is genetically associated with the common late onset familial and sporadic forms of Alzheimer9s disease (AD). Risk for AD increased from 20% to 90% and mean age at onset decreased from 84 to 68 years with increasing number of APOE-epsilon 4 alleles in 42 families with late onset AD. Thus APOE-epsilon 4 gene dose is a major risk factor for late onset AD and, in these families, homozygosity for APOE-epsilon 4 was virtually sufficient to cause AD by age 80.

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Topics: Late onset (69%), APOE*4 Allele (56%), SORL1 (54%) ...read more

8,099 Citations


Journal ArticleDOI: 10.1177/0192623307313011
Abstract: Air pollution is a serious environmental problem. We investigated whether residency in cities with high air pollution is associated with neuroinflammation/neurodegeneration in healthy children and young adults who died suddenly. We measured mRNA cyclooxygenase-2, interleukin-1beta, and CD14 in target brain regions from low (n = 12) or highly exposed residents (n = 35) aged 25.1 +/- 1.5 years. Upregulation of cyclooxygenase-2, interleukin-1beta, and CD14 in olfactory bulb, frontal cortex, substantia nigrae and vagus nerves; disruption of the blood-brain barrier; endothelial activation, oxidative stress, and inflammatory cell trafficking were seen in highly exposed subjects. Amyloid beta42 (Abeta42) immunoreactivity was observed in 58.8% of apolipoprotein E (APOE) 3/3 < 25 y, and 100% of the APOE 4 subjects, whereas alpha-synuclein was seen in 23.5% of < 25 y subjects. Particulate material (PM) was seen in olfactory bulb neurons, and PM < 100 nm were observed in intraluminal erythrocytes from lung, frontal, and trigeminal ganglia capillaries. Exposure to air pollution causes neuroinflammation, an altered brain innate immune response, and accumulation of Abeta42 and alpha-synuclein starting in childhood. Exposure to air pollution should be considered a risk factor for Alzheimer's and Parkinson's diseases, and carriers of the APOE 4 allele could have a higher risk of developing Alzheimer's disease if they reside in a polluted environment.

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Topics: Neuroinflammation (54%), Apolipoprotein E (53%), APOE*4 Allele (53%) ...read more

599 Citations


Open accessJournal ArticleDOI: 10.1523/JNEUROSCI.17-02-00516.1997
Abstract: A relationship between the apolipoprotein E (apoE) genotype and the risk to develop Alzheimer's disease has been established recently. Apolipoprotein synthesis is implicated in developmental processes and in neuronal repair of the adult nervous system. In the present study, we investigated the influence of the apolipoprotein polymorphism on the severity of neuronal degeneration and the extent of plastic dendritic remodeling in Alzheimer's disease. Changes in length and arborization of dendrites of Golgi-impregnated neurons in the basal nucleus of Meynert, locus coeruleus, raphe magnus nucleus, medial amygdaloid nucleus, pedunculopontine tegmental nucleus, and substantia nigra were analyzed after three-dimensional reconstruction. Patients with either one or two apoE epsilon 4 alleles not only showed a more severe degeneration in all areas investigated than in patients lacking the apoE 4 allele but also revealed significantly less plastic dendritic changes. ApoE epsilon 4 allele copy number, furthermore, had a significant effect on the pattern of dendritic arborization. Moreover, the relationship between the intensity of dendritic growth and both the extent of neuronal degeneration and the stage of the disease seen in patients lacking the apoE epsilon 4 allele was very weak in the presence of one epsilon 4 allele and completely lost in patients homozygous for the epsilon 4 allele. The results provide direct evidence that neuronal reorganization is affected severely in patients with Alzheimer's disease carrying the apoE epsilon 4 allele. This impairment of neuronal repair might lead to a more rapid functional decompensation, thereby contributing to an earlier onset and more rapid progression of the disease.

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Topics: APOE*4 Allele (74%), Apolipoprotein E (62%), Locus coeruleus (52%) ...read more

305 Citations


Open accessJournal ArticleDOI: 10.1093/AJCN/87.2.449
Lawrence J. Whalley1, Ian J. Deary2, John M. Starr2, Klaus W Wahle  +3 moreInstitutions (2)
Abstract: Background: Evidence for an inverse relation between dietary intake of n–3 polyunsaturated fatty acids (PUFAs) and age-related cognitive decline is inconsistent. This inconsistency may arise becausetherelationispresentonlyintheabsenceoftheapolipoprotein E 4( APOE 4) allele. Objective: We aimed to determine the contribution of erythrocyte n–3 PUFA content to cognitive aging in the presence or absence of the APOE 4 allele. Design: We followed up 120 volunteers, born in 1936, at approximate ages of 64, 66, and 68 y. Their intelligence quotient at 11 y old was available. At first follow-up, we determined APOE genotype and measured the PUFA composition of erythrocyte membranes. Six cognitive tests were administered at all follow-ups. We related cognitiveperformanceat64yoldandcognitivechangesfrom64 to 68 y old to erythrocyte n–3 PUFA composition on recruitment and to APOE 4 allele status. Results:Totaln–3PUFAanddocosohexaenoicacidconcentrations were associated with benefits for cognition at 64 y old and from 64 to 68 y old. After adjustment for sex, APOE 4 status, and intelligencequotientat11yold,theeffectsassociatedwithtotaln–3 PUFAremainedsignificant.Cognitivebenefitswereassociatedwith higher erythrocyte n–3 PUFA content but were significant only in the absence of the APOE 4 allele. Conclusions: These data are evidence of a gene environment interaction for cognitive aging. They are relevant to the analysis of trials of n–3 PUFA supplements in cognitive aging and dementia prevention, and they support heterogeneity in cognitive aging and, possibly, in Alzheimer disease. Am J Clin Nutr 2008;87:449–54.

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Topics: APOE*4 Allele (67%), Cognitive decline (57%), Apolipoprotein E (54%)

165 Citations


Journal ArticleDOI: 10.1111/J.1532-5415.1998.TB01532.X
Abstract: OBJECTIVE This study investigated whether the Apolipoprotein (APOE) epsilon4 allele was associated with cognitive decline in community-dwelling older adults. DESIGN Longitudinal cognitive performance of older adults with the epsilon3/epsilon4 genotype was compared with that of older adults with the epsilon3/epsilon3 genotype. SETTING Aging Clinical Research Center, Stanford University. PARTICIPANTS One hundred community-dwelling older adults were recruited from a pool of 531 individuals who had participated in a memory training study 4 to 5 years earlier. These individuals were concerned about their memory functioning and were recruited through newspaper advertisements and contacts with local senior centers. The 100 individuals who agreed to participate in the follow-up investigation were between 59 and 95 years of age. MEASUREMENTS At both baseline and follow-up, subjects were administered a battery of seven cognitive tests that examined verbal and spatial memory, attention, speed-of-processing, and language abilities. APOE genotype was determined at follow-up. RESULTS Individuals with the epsilon3/epsilon4 APOE genotype were significantly younger than individuals with the APOE epsilon3/epsilon3 genotype. No significant differences were observed between the two groups on measures of attention, speed-of-processing, vocabulary, immediate verbal memory, and immediate spatial memory. However, those older adults with the epsilon3/epsilon4 genotype exhibited significantly greater decline in performance on delayed recall of verbal material than did those with the epsilon3/epsilon3 APOE genotype. CONCLUSION These findings are consistent with previous studies, which suggest that the APOE epsilon4 allele predicts decline on measures of delayed recall.

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Topics: APOE*4 Allele (61%), Cognitive decline (57%), Verbal memory (56%) ...read more

122 Citations


Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20191
20172
20164
20153
20142
20132

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Topic's top 5 most impactful authors

Ian J. Deary

3 papers, 248 citations

M. Ilyas Kamboh

3 papers, 177 citations

John M. Starr

3 papers, 248 citations

Zoltán Janka

2 papers, 3 citations

Yvette P. Conley

2 papers, 114 citations

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