• Molecules and Cells
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• 제42권11호
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• pp.739-746
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• 2019

Significant knowledge about the pathophysiology of Alzheimer's disease (AD) has been gained in the last century; however, the understanding of its causes of onset remains limited. Late-onset AD is observed in about 95% of patients, and APOE4-encoding apolipoprotein E4 (ApoE4) is strongly associated with these cases. As an apolipoprotein, the function of ApoE in brain cholesterol transport has been extensively studied and widely appreciated. Development of new technologies such as human-induced pluripotent stem cells (hiPSCs) and CRISPR-Cas9 genome editing tools have enabled us to develop human brain model systems in vitro and readily manipulate genomic information. In the context of these advances, recent studies provide strong evidence that abnormal cholesterol metabolism by ApoE4 could be linked to AD-associated pathology. In this review, we discuss novel discoveries in brain cholesterol dysregulation by ApoE4. We further elaborate cell type-specific roles in cholesterol regulation of four major brain cell types, neurons, astrocytes, microglia, and oligodendrocytes, and how its dysregulation can be linked to AD pathology.

• 대한한의학회지
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• 제25권4호
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• pp.209-219
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• 2004

The author investigated whether ACE/DD, AGN/TT, and ApoE/ε4 genotypes are associated with CI and whether genetic risk is enhanced by Sasang constitutional classification. The author ascertained these genotypes in patients with CI (n=211), diagnosed by brain computed tomography. Control subjects for the infarction group were randomly selected from 319 subjects matched for age, gender, and history of hypertension with patients. The ACE/DD genotype was not associated with CI. However. there was significant association between ApoE polymorphism and CI (x²=15.089, p<.05). Furthermore, frequency of AGN/TT genotype was higher in the patients with CI than in the controls (x²=20.072, p<.05). The frequency of T allele Was 0.91 in patients and 0.82 in controls (x²=17.237, p<.05). However, the Sasang constitutional classification did not increase the relative risk for CI in the subjects with ApoE/ε4 or AGN/T allele. These results suggest that ApoE and AGN polymorphism predict CI. but Sasang constitutional classification does not enhance the risk for CI associated with ApoE/ε4 or AGN/TT in a Korean population.

• Journal of Korean Neurosurgical Society
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• 제39권1호
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• pp.46-51
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• 2006

Objective : An Intracranial aneurysm is an important acquired cerebrovascular disease that can cause a catastrophic subarachnoid hemorrhage. Atherosclerosis is one of possible mechanism, but its contribution to aneurysm formation is unclear. Human apolipoprotein E[apoE] is best known for its arterial protection from atherosclerosis. In this study we observe apoE expression in experimental cerebral aneurysms of rats to elucidate the role of apoE in the process of cerebral aneurysm formation. Methods : Twenty-four male 7-week-old Sprague-Dawley strain rats received a cerebral aneurysm induction procedure. One month[12] and three months[12] after the operation, the rats were killed, their cerebral arteries were dissected, and the regions of the bifurcation of the right anterior cerebral artery-olfactory artery [ACA-OA] bifurcations were examined histologically and immunohistochemically. Results : In the 1 month group [n=12], the ACA-OA bifurcation showed no aneurysmal change in 7 rats and early aneurysmal change in 5 rats. In the 3 months group (n=12), the bifurcation showed no aneurysmal change in 2 rats and an advanced aneurysm in 10 rats. ApoE expression were in 3 specimen in early aneurysmal change, but not in advanced aneurysms. Conclusion : ApoE expression in early aneurysmal wall suggests a possible role for apoE in early events leading to aneurysm formation. Further studios are necessary to elucidate the exact role of apoE in the pathophysiology of cerebral aneurysm.

• Fisheries and Aquatic Sciences
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• 제11권2호
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• pp.88-97
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• 2008

Lipoproteins are complexes of lipids and specific apolipoproteins that are involved in lipid transport and redistribution among various tissues. In this study, we isolated full-length apolipoprotein cDNA sequences encoding apolipoprotein A-I (apoA-I), apoE, apoC-II, and apo-14 kDa in barred knifejaw, Oplegnathus fasciatus. In addition, we reconstructed phylogenetic trees and investigated mRNA tissue distributions. Alignment analyses of amino acid sequences revealed that secondary structures of the polypeptides apoA-I, apoE, and apoC-II in barred knifejaw are well conserved with their teleostean and mammalian counterparts in terms of characteristic tandem repetitive units forming amphipathic ${\alpha}$-helices. Both the sequence alignment data and cleavage sites of apo-14 kDa indicated a clear differentiation between Percomorpha and Cypriniformes. Meanwhile, the phylogenetic trees of apolipoprotein sub-families suggested that the common ancestor prior to the split of the Actinopterygii (ray-finned fishes) and Sarcopterygii (tetrapods) would have possessed the primordial protein-encoding genes. Tissue distribution of each apolipoprotein transcript determined by semi-quantitative RTPCR showed that barred knifejaw apoA-I transcripts were more or less ubiquitously expressed in the liver, intestines, brain, muscle, spleen, and kidney. The most striking difference from previous observations on barred knifejaw was the ubiquitous expression of apoE across all somatic tissues. Barred knifejaw apoC-II showed tissue-specific expression in the liver and intestines, while the liver and brain were the major sites of apo-14kDa mRNA synthesis.

• 한국산학기술학회논문지
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• 제21권1호
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• pp.477-486
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• 2020

본 연구는 알츠하이머 치매노인을 대상으로 Apolipoprotein E (ApoE) ɛ4의 유무와 치매수준에 따른 우울과 기억력의 상관관계를 분석하고자 하였다. 임상치매척도(clinical dementia rating; CDR)가 0.5점에서 2점 사이인 65세 이상 노인 50명을 대상으로 임상치매척도, 노인용 서울언어학습검사, 레이 복합도형검사, 축약형 노인우울검사를 실시하였고 ApoE 유전자형은 구강상피세포를 채취하여 실시한 유전자 검사를 통해 확인하였다. 자료분석은 맨 휘트니 U 검정, 상관관계 분석을 실시하였다. ApoE ɛ4가 없는 경우에 CDR 1점과 2점에서 우울과 언어적 즉시회상 기억력이 유의한 음의 상관관계가 있었고(p<.05), ApoE ɛ4를 보유한 경우에는 CDR 1점에서 우울과 언어적 즉시회상, 언어적 지연회상 기억력에서 유의한 음의 상관관계가 있었다(p<.05). 우울과 언어적 즉시회상 기억력은 유의한 상관관계가 있었고 ApoE ɛ4를 보유한 경우에는 우울과 언어적 지연회상 기억력에도 유의한 상관관계가 있었다. 따라서 알츠하이머 치매의 예방 및 중재로 시각적인 훈련보다 언어적 기억력훈련이 유용할 것이며 우울치료가 상호보완적으로 도움을 줄 수 있을 것으로 기대한다.

• Journal of Preventive Medicine and Public Health
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• 제43권3호
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• pp.213-221
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• 2010

Objectives: Plasma lipid profiles and Apolipoprotein E (ApoE) are established risk factors for cardiovascular disease (CVD). The knowledge of lipid profile may estimate the potential victims of cardiovascular disease before its initiation and progression and offers the opportunity for primary prevention. The most common ApoE polymorphism has been found to influence plasma lipid concentrations and its correlation with CVD has been extensively investigated in the last decade. Methods: The ApoE polymorphism and its influence on plasma lipid were investigated in healthy woman workers. The information on confounding factors was obtained through a self-administered questionnaire and ApoE polymorphism was investigated using PCR. Results: The relative frequencies of alleles E2, E3 and E4 for the study population (n = 305) were 0.127, 0.750 and 0.121, respectively. ApoE polymorphism was associated with variations in plasma HDL-cholesterol lipid profile. In order to estimate the independent effects of alleles E2 and E4, as compared with E3, on lipid profile, multiple regression was performed after adjustment for confounding variables such as age, BMI, blood pressure, education status, insulin, fasting glucose, HOMA-IR, menopause. ApoE2 had a negative association with HDL cholesterol and ApoE4 had a positive association with LDL cholesterol. Conclusions: This study identified that the ApoE and CVD risk factors contribute to the lipid profiles, similar to other studies. The analysis including dietary intake and other gene in further studies may help to identify clear effects on lipid profiles as risk factor for CVD.

• 생물정신의학
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• 제15권1호
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• pp.29-34
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• 2008

Objectives : This study aimed to test potential modifying effects of education on the association between apolipoprotein E ${\varepsilon}4$ (Apo E4) and cognitive decline. Methods : A community cohort(N=683) aged 65 or over completed the Korean version of Mini-Mental State Examination(MMSE-K) at baseline and two years later(1999-2001). Apo E polymorphisms were genotyped, and classified into that with or without Apo E4. Educational levels were categorized into people with or without education. Covariates included demographic(age, gender), life style(smoking, alcohol drinking), clinical (depression, sleep disorder, vascular risk factors) characteristics. Results : The association between Apo E4 and cognitive decline was significant only in the old persons with no education. The interaction term between education and Apo E4 on cognitive decline was significant(p=0.040). Conclusion : Elders with no education might be more vulnerable to the impact of Apo E4 on cognitive decline, which suggests gene-environment interaction.

• Asian-Australasian Journal of Animal Sciences
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• 제9권5호
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• pp.515-517
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• 1996

The relative efficiencies of deposition into egg yolk of apo-carotenoic acid ester(APO-E, CAROPHYLL Yellow) and saponified marigold xanthophylls (MX), in the presence of canthaxanthin (CN), were determined using a wheat-based diet. APO-E was deposited with an efficiency of 50 percent and MX with an efficiency between 13 and 20 percent. The dose response relationship for MX was curvilinear with a decreased efficiency at higher concentrations. Canthaxanthin was deposited with and efficiency of 38 percent, irrespective of the source of yellow xanthophylls, up to a dietary concentration of 5.5 mg/kg. At a dietary MX concentration of 8.3 mg/kg the efficiency of deposition of CN declined to 24 percent. The results confirm that the replacement ratio of MX : APO-E is between 3 : 1 and 4 : 1 depending on the dietary inclusion of marigold pigment.

• Advances in Traditional Medicine
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• 제6권4호
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• pp.312-318
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• 2006

The association between apolipoprotein E (apoE) gene polymorphism and ischemic cerebrovascular disease (ICVD) has been controversial. These controversies may be due to inaccurate classification of patients and ethnic differences. The aim of the present study was to assess the relationship between apoE gene polymorphism and the development of ICVD in a population from Korea. We investigated 136 patients with ICVD and 357 controls without ICVD. No differences in the apoE genotypes frequencies ($X^{2}$ = 3.660, df = 5, P = 0.454) and even in the alleles frequencies ($X^{2}$ = 1.946, df = 2, P = 0.378) were observed in the ICVD patients compared with that in controls. The data have been compared with data found in other population groups. However, the risk of ICVD associated with apoE ${\varepsilon}3/{\varepsilon}4$ genotype was increased nearly 3-fold in subjects possessing the history of diabetes mellitus (OR 3.3, 95% CI 1.2-9.4, P = 0.026). We concluded that the apoE polymorphism is not associated with ICVD at least in the Korean population, but the apoE frequencies found in this study differ significantly from those obtained in Japanese.

• 생약학회지
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• 제44권4호
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• pp.397-401
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• 2013

The Galkun-Whanglyeon-Whanggum-Tang, an officially standardized mixture of traditional herbal medicines used in Korea and China, consists of Pueraria lobata, Scullellaria baicalensis, Coptis chinensis and Glycyrrhiza uralensis at a ratio of 6:9:3:2.4. In this study, we evaluated the effect of lowering lipid accumulation in blood by treatment of Galkun-Whanglyeon-Whanggum-Tang in Apo E(-/-) atherosclerotic animal model. ApoE/mice fed with 1.25% cholesterol, 7.5% cocoa butter and 0.5% sodium cholate diet were orally given vehicle or Galkun-Whanglyeon-Whanggum-Tang(10, 100 and 300 mg/kg/day) for 12 weeks. Serum levels of triglyceride(TG), total cholestrerol(TC), low-density lipoprotein(LDL) and high-density lipoprotein(HDL) were analyzed, and PPAR-${\alpha}$ and PPAR-${\gamma}$ were examined by Western blotting analysis. Galkun-Whanglyeon- Whanggum-Tang decreased serum levels of TG, TC and LDL, but not HDL in ApoE/mice. In parallel, Galkun-Whanglyeon-Whanggum-Tang treatment showed the increased activity of PPAR-${\alpha}$ and PPAR-${\gamma}$ in hepatocytes. In summary, Galkun-Whanglyeon-Whanggum-Tang can reduce lipid accumulation in blood, and this effect might be accompanied by the upregulation of PPAR-${\alpha}$ and PPAR-${\gamma}$ in Apo E(-/-) atherosclerotic mouse model.