• 생물정신의학
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• 제20권3호
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• pp.104-110
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• 2013

Objectives : The aim of this study was to examine the prospective impact of the apolipoprotein E (APOE) ${\varepsilon}4$ on cognitive performance in the community-dwelling elderly individuals with Alzheimer's disease (AD). Methods : The total number of subjects was 30 (12 men and 18 women) who were diagnosed with AD from a Korean project of "Early Detection of Dementia". People aged 65-85 years were included in the analysis. The eight neuropsychological domains from the Korean version of Consortium to Establish a Registry of Alzheimer's Disease (CERAD-K) were conducted to test subjects. They have been followed at 24-month intervals with the same assessments at each interval. Their cognitive performance at 2 year intervals was compared by the occurrence of the APOE ${\varepsilon}4$. Results : The impact of ${\varepsilon}4$ allele was significant in the Word List Memory Test (WLMT, F = 4.345, df = 1, p = 0.021) and Word List Recall Test (WLRT, F = 5.569, df = 1, p = 0.033). Conclusions : The APOE ${\varepsilon}4$ allele was significantly correlated especially with verbal episodic memory domain in community-dwelling elders diagnosed with AD.

• 생물정신의학
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• 제13권2호
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• pp.103-109
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• 2006

Objective : Associations of vascular risk/disease or apolipoprotein E ${\varepsilon}4$(APOE4) with geriatric depression has been unclear at a population level. This study aimed to evaluate whether there would be interactions of vascular risk/disease and APOE4 on depression in a Korean elderly population. Methods : 732 community residents aged 65 or over were assessed for depression(GMS), information on vascular risk/disease(reported stroke, transient ishemic attack, heart disease, hypertension, diabetes, smoking), examinations for vascular risk/disease(blood pressure, blood tests for glucose and lipid profiles, body size), APOE genotypes, demographic characteristics(age, gender, education), physical health, and cognitive function(MMSE). Results : Previous stroke and lower level of high density lipoprotein(HDL) cholesterol were significantly associated with geriatric depression independent of demographic characteristics, physical illnesses, and cognitive function. These associations were statistically significant only in those with APOE4, although the interaction terms didn't reach to statistical significance. Conclusion : Associations between vascular risk/disease and geriatric depression might be more prominent in those with APOE4. However further research would be needed to clarify this issue.

• 한국축산식품학회지
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• 제29권1호
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• pp.108-113
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• 2009

포유동물의 혈장 지단백의 일종인 apolipoprotein E (APOE)는 인지질 및 트리글리세라이드와 같은 지질과 콜레스테롤의 대사와 운반에 중요한 기능을 담당한다. 본 연구는 지질대사조절 관련 후보유전자로서 APOE 유전자를 대상으로 한우에서 이 유전자의 SNP를 탐색 발굴하고 SNP 유전자형이 육량 및 육질 등 도체형질에 미치는 영향을 분석하기 위하여 수행하였다. 먼저 혈연관계가 없는 한우 60두의 pooled DNA를 제작하여 APOE 유전자의 exon 4 영역을 포함하는 primer를 설계하여 PCR로 증폭한 결과 exon 4 영역내 2034번째 T>C 염기치환에 의한 SNP를 검출하였다. 후대검정우 총 309두에 대한 검정 개체별 SNP 유전자형을 판정하기 위하여 Acc I 제한효소를 이용하여 PCR-RFLP기법으로 분석한 결과 SNP 유전자형 출현빈도는 TT형 10.9%, TC형 46.9% 및 CC형 42.2%로 나타났으며, T와 C 대립유전자빈도는 각각 0.344와 0.656으로 추정되었다. 또한 APOE 유전자의 SNP 유전자형과 육량 및 육질 등 도체형질과의 연관성을 통계 분석한 결과 도체율 및 육색형질과의 유의적 연관성이 입증되었다. 즉, TT형을 가진 개체들이 CC형을 가진 개체들에 비해 도체율 값이 유의적으로 높았다(p<0.05). 또한 육색에서도 TT형을 가진 개체들이 CC형을 가진 개체들에 비해 좀 더 바람직한 육색을 나타내었다. 따라서 본 연구에서 검출한 한우 APOE 유전자의 SNP 유전자형은 한우의 육량지수 평가 및 도체율이 높은 개체선발을 위한 DNA marker로 활용 가능할 것으로 기대된다.

• 생물정신의학
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• 제17권4호
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• pp.218-225
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• 2010

Objectives : The potential association between choline acetyltransferase(CHAT) polymorphism and the risk of mild cognitive impairment(MCI) has not been investigated in Korea. We examined the main effect of CHAT polymorphism and its interaction with apolipoprotein E(APOE) polymorphism in the development of MCI in elderly Korean sample. Methods : We analyzed CHAT 2384G > A polymorphism and APOE polymorphism among 149 MCI subjects with MCI and 298 normal controls. We tested the association between MCI and CHAT A allele status using a logistic regression model. In addition, we employed generalized multifactor dimensionality reduction(GMDR) to investigate the interaction between CHAT and APOE with regard to the risk of MCI. Results : The CHAT A allele was associated with AD risk(OR = 1.59, 95% CI = 1.02-2.48, p = 0.042). No significant gene-gene interaction between CHAT and APOE was found in GMDR method(testing balanced accuracy = 0.540, p = 0.055). Conclusion : The CHAT A allele was associated with MCI risk in the Korean elderly. Its interaction with the APOE ${\varepsilon}4$ allele was not significant with regard to the development of MCI.

• 생물정신의학
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• 제15권1호
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• pp.5-13
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• 2008

Objectives : It was the aim of the present paper to examine the impact of the apolipoprotein E(APOE) ${\varepsilon}4$ on cognitive performance in community-dwelling elderly samples with 'questionable dementia'. Methods : Total 295 samples who were diagnosed with 'questionable dementia' in the recent year and completed the Korean version of the Consortium Establish a Registry for Alzheimer's Disease(CERAD-K) neuropsychological assessment protocol, were recruited. The CDR test established score of 0.5. Genomic DNA was extracted from the venous blood and APOE genotyping was done in this group. Their cognitive performance was compared by the occurrence of the APOE ${\varepsilon}4$ allele. Results : The impact of ${\varepsilon}4$ allele was significant in the Word List Recall Test(WLRT, F=4.511, df=1, p=0.035). The 'young-old' group aged 75 years and under had a significantly lower performance on the Word List Recall Test(WLRT, F=5.090, df=1, p=0.015), but the 'old-old' group over 75 years of age had not significantly different performance on the all the item of tests in ${\varepsilon}4$+ allele group. Conclusion : The conclusion to be drawn here is that community-dwelling elderly samples with ${\varepsilon}4$ allele in 'questionable dementia' had a significantly lower performance on the Word List Recall Test in the CERAD-K neuropsychological test batteries and the effect was prominent in the 'young-old' age group.

• 대한임상검사과학회지
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• 제36권2호
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• pp.110-114
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• 2004

Apolipoprotein E is the major lipid-carrier protein in the brain, and several studies provided evidence that apolipoprotein E(ApoE) epsilon4 allele can be considered a genetic risk factor for Alzheimer's disease(AD). Inheritance of the APOE gene has three alleles: ${\varepsilon}2$, ${\varepsilon}3$ and ${\varepsilon}4$. There are six possible genotypes: ${\varepsilon}2/{\varepsilon}2$, ${\varepsilon}3/{\varepsilon}3$, ${\varepsilon}4/{\varepsilon}4$, ${\varepsilon}2/{\varepsilon}3$, ${\varepsilon}2/{\varepsilon}4$, ${\varepsilon}3/{\varepsilon}4$. AD is characterized by a progressive loss of function and death of nerve cells in several areas of the brain. The ${\varepsilon}4$ allele is associated with a risk for developing AD. People with the ${\varepsilon}4/{\varepsilon}4$ genotype have the highest risk, but people with the ${\varepsilon}2/{\varepsilon}4$ or ${\varepsilon}3/{\varepsilon}4$ genotypes are also likely to develop the disease. 64.3% of people carry the is ${\varepsilon}3/{\varepsilon}3$ genotype, 22.1% carry the second ${\varepsilon}3/{\varepsilon}4$ genotype but, ${\varepsilon}2/{\varepsilon}2$ genotype is not usually found of people carry the 3.6% is ${\varepsilon}4/{\varepsilon}4$ genotype in a total of a test group of 140 people. The ratio of ${\varepsilon}4/{\varepsilon}4$ genotype related directly with AD is less than the ${\varepsilon}3/{\varepsilon}3$ genotype, but the ${\varepsilon}2/{\varepsilon}4$ and ${\varepsilon}3/{\varepsilon}4$ genotype ratio of indirect AD risk is 25.7% in the group of people, regardless. Thus, we have referred to the benefit from the treatment of AD through apoE genotype diagnosis.

• 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.

• 생물정신의학
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• 제21권4호
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• pp.115-117
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• 2014

Variety of biomarkers that are related to the Alzheimer's disease and its diagnosis and progress have been found. However, research lacks in predicting the reaction of the treatment. In addition, there is no definite treatment reaction to the disease but rather it is varied. The purpose of this review article is to study the research of the biomarkers that are able to predict the treatment reaction. There was a research that illustrated a relationship between plasma amyloid ${\beta}$ peptide, cerebrospinal fluid tau, neuroanatomical biomarkers and acetylcholinesterase inhibitors. Polymorphisms in genes of the cholinergic markers AChE, BuChE, ChAT and PON-1 were found to be associated with better clinical response to acetylcholinesterase inhibitors. Many pharmacogenetic studies have been conducted to evaluate the impact of the lipoprotein apolipoprotein E (APOE) genotype on treatment response to acetylcholinesterase inhibitor. However, there is no significant influence of the APOE genotypes on treatment response. Further research is needed to find other predictors of treatment with acetylcholinesterase inhibitors in patients with Alzheimer's disease.

• Molecules and Cells
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• 제37권11호
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• pp.767-776
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• 2014

Alzheimer's disease (AD) is clinically characterized with progressive memory loss and cognitive decline. Synaptic dysfunction is an early pathological feature that occurs prior to neurodegeneration and memory dysfunction. Mounting evidence suggests that aggregation of amyloid-${\alpha}$ ($A{\alpha}$) and hyperphosphorylated tau leads to synaptic deficits and neurodegeneration, thereby to memory loss. Among the established genetic risk factors for AD, the ${\varepsilon}4$ allele of apolipoprotein E (APOE) is the strongest genetic risk factor. We and others previously demonstrated that apoE regulates $A{\alpha}$ aggregation and clearance in an isoform-dependent manner. While the effect of apoE on $A{\alpha}$ may explain how apoE isoforms differentially affect AD pathogenesis, there are also other underexplored pathogenic mechanisms. They include differential effects of apoE on cerebral energy metabolism, neuroinflammation, neurovascular function, neurogenesis, and synaptic plasticity. ApoE is a major carrier of cholesterols that are required for neuronal activity and injury repair in the brain. Although there are a few conflicting findings and the underlying mechanism is still unclear, several lines of studies demonstrated that apoE4 leads to synaptic deficits and impairment in long-term potentiation, memory and cognition. In this review, we summarize current understanding of apoE function in the brain, with a particular emphasis on its role in synaptic plasticity and the underlying cellular and molecular mechanisms, involving low-density lipoprotein receptor-related protein 1 (LRP1), syndecan, and LRP8/ApoER2.

• BMB Reports
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• 제53권5호
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• pp.284-289
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• 2020

Tamoxifen, a nonsteroidal estrogen receptor (ER) antagonist, is used routinely as a chemotherapeutic agent for ER-positive breast cancer. However, it is also causes side effects, including retinotoxicity. The retinal pigment epithelium (RPE) has been recognized as the primary target of tamoxifen-induced retinotoxicity. The RPE plays an essential physiological role in the normal functioning of the retina. Nonetheless, potential therapeutic agents to prevent tamoxifen-induced retinotoxicity in breast cancer patients have not been investigated. Here, we evaluated the action mechanisms of sulfasalazine against tamoxifen-induced RPE cell death. Tamoxifen induced reactive oxygen species (ROS)-mediated autophagic cell death and caspase-1-mediated pyroptosis in RPE cells. However, sulfasalazine reduced tamoxifen-induced total ROS and ROS-mediated autophagic RPE cell death. Also, mRNA levels of tamoxifen-induced pyroptosis-related genes, IL-1β, NLRP3, and procaspase-1, also decreased in the presence of sulfasalazine in RPE cells. Additionally, the mRNA levels of tamoxifen-induced AMD-related genes, such as complement factor I (CFI), complement factor H (CFH), apolipoprotein E (APOE), apolipoprotein J (APOJ), toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4), were downregulated in RPE cells. Together, these data provide novel insight into the therapeutic effects of sulfasalazine against tamoxifen-induced RPE cell death.