• 제목/요약/키워드: s disease (AD)

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Searching for blue ocean of Alzheimer's disease drug discovery

  • 묵인희
    • 한국응용약물학회:학술대회논문집
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    • 한국응용약물학회 2006년도 Spring Conference
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    • pp.109-120
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    • 2006
  • Alzheimer's disease (AD) is an age-related neurodegenerative disorder. The pathological hallmarks of AD are senile plaques and neurofibrillary tangles in the brain. Major component of senile plaques is amyloid beta peptide(A$\beta$) which is derived from amyloid precursor protein (APP). A$\beta$ is generated through the sequential cleavage of App by $\beta$ - and $\gamma$-secretases. $\beta$-secretase excises the ectodomain of APP ($\beta$-APPs) to leave a 99-amino acid long C-terminal fragment (APP-C99-CTF) in the membrane. $\gamma$-secretase then cleaves this membrane-tethered APP-CTF within the transmembrane domain, so releasing A$\beta$ peptides and APP-intracellular domain (AICD). Thus, $\beta$- and $\gamma$-secretase are regarded to perform the key steps in the pathogenesis of AD and have become important therapeutic targets in the prevention and treatment of AD. Enormous efforts have been focused to develop the amyloid beta related drug for cure of AD becuase A$\beta$ is believed to be one of the major causes of AD. since major pharmaceutical companies in world wide base compete to develop new drug for AD, we have to be careful to choose the drug target to success the tough race. In the present talk, possible drug targets based on basic research results will be discussed. These molecules should be a good target for development of new drug for AD and be less competitive to have a good shape for world wide competition.

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Comparison of Cerebral Cortex Transcriptome Profiles in Ischemic Stroke and Alzheimer's Disease Models

  • Juhyun Song
    • Clinical Nutrition Research
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    • 제11권3호
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    • pp.159-170
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    • 2022
  • Ischemic stroke and Alzheimer's disease (AD) are representative geriatric diseases with a rapidly increasing prevalence worldwide. Recent studies have reported an association between ischemic stroke neuropathology and AD neuropathology. Ischemic stroke shares some similar characteristics with AD, such as glia activation-induced neuroinflammation, amyloid beta accumulation, and neuronal cell loss, as well as some common risk factors with AD progression. Although there are considerable similarities in neuropathology between ischemic stroke and AD, no studies have ever compared specific genetic changes of brain cortex between ischemic stroke and AD. Therefore, in this study, I compared the cerebral cortex transcriptome profile of 5xFAD mice, an AD mouse model, with those of middle cerebral artery occlusion (MCAO) mice, an ischemic stroke mouse model. The data showed that the expression of many genes with important functional implications in MCAO mouse brain cortex were related to synaptic dysfunction and neuronal cell death in 5xFAD mouse model. In addition, changes in various protein-coding RNAs involved in synaptic plasticity, amyloid beta accumulation, neurogenesis, neuronal differentiation, glial activation, inflammation and neurite outgrowth were observed. The findings could serve as an important basis for further studies to elucidate the pathophysiology of AD in patients with ischemic stroke.

아토피 피부염 환아의 정신 건강 분석 및 아토피 피부염 교육을 통한 인식, 인지도 개선에 대한 고찰 (A Study on Mental Health Analysis of Atopic Children and Awareness Improvement through Atopic Education)

  • 박승구;노현민;조은희;박민철
    • 한방안이비인후피부과학회지
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    • 제30권2호
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    • pp.51-85
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    • 2017
  • Objectives : This study aimed to investigate the awareness improvement of atopic dermatitis(AD) for AD children's parents and to evaluate the mental health condition of AD children and QoL of their parents. Methods : We conducted elementary school visit education(the first education) and recruited children and parents who wanted to participate the hospital visit education(the Second education). In the first education, we lectured about AD, performed survey about QoL and awareness about AD and obtained 48 valid results. In the second education, we performed an education for AD again, skin condition evaluation, mental health analysis survey and obtained 29 valid results. We compared the AD and non-AD groups of each education in the first and second education. We assessed atopic awareness, FDLQI, DFI, CDI, BAI, and KISE scores by gender, age, duration of disease, onset, and severity of AD. Results : Despite children with AD, the survey showed their parents lacked knowledge about AD. However, they acquired the necessary knowledge in AD education. There was a significant difference in the total score of Atopic awareness between the AD group in the first education and the AD group in the second education. (p=0.042) In addition, the CDI and BAI scores of all patients were divided by the duration of disease, and it was estimated that depression and anxiety disorders may be aggravated by longer term illness. Conclusions and Discussions : This study confirmed duration of AD affects AD children's mental health, and verified positive changes in atopic awareness after AD education.

Month and Season of Birth as a Risk Factor for Alzheimer's Disease: A Nationwide Nested Case-control Study

  • Tolppanen, Anna-Maija;Ahonen, Riitta;Koponen, Marjaana;Lavikainen, Piia;Purhonen, Maija;Taipale, Heidi;Tanskanen, Antti;Tiihonen, Jari;Tiihonen, Miia;Hartikainen, Sirpa
    • Journal of Preventive Medicine and Public Health
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    • 제49권2호
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    • pp.134-138
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    • 2016
  • Objectives: Season of birth, an exogenous indicator of early life environment, has been related to higher risk of adverse psychiatric outcomes but the findings for Alzheimer's disease (AD) have been inconsistent. We investigated whether the month or season of birth are associated with AD. Methods: A nationwide nested case-control study including all community-dwellers with clinically verified AD diagnosed in 2005 to 2012 (n=70 719) and up to four age- sex- and region of residence-matched controls (n=282 862) residing in Finland. Associations between month and season of birth and AD were studied with conditional logistic regression. Results: Month of birth was not associated with AD (p=0.09). No strong associations were observed with season (p=0.13), although in comparison to winter births (December-February) summer births (June-August) were associated with higher odds of AD (odds ratio, 1.03; 95% confidence interval, 1.00 to 1.05). However, the absolute difference in prevalence in winter births was only 0.5% (prevalence of those born in winter were 31.7% and 32.2% for cases and controls, respectively). Conclusions: Although our findings do not support the hypothesis that season of birth is related to AD/dementia risk, they do not invalidate the developmental origins of health and disease hypothesis in late-life cognition. It is possible that season does not adequately capture the early life circumstances, or that other (postnatal) risk factors such as lifestyle or socioeconomic factors overrule the impact of prenatal and perinatal factors.

Diagnosis of Alzheimer's Disease using Wrapper Feature Selection Method

  • 비슈나비 라미네니;권구락
    • 스마트미디어저널
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    • 제12권3호
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    • pp.30-37
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    • 2023
  • Alzheimer's disease (AD) symptoms are being treated by early diagnosis, where we can only slow the symptoms and research is still undergoing. In consideration, using T1-weighted images several classification models are proposed in Machine learning to identify AD. In this paper, we consider the improvised feature selection, to reduce the complexity by using wrapping techniques and Restricted Boltzmann Machine (RBM). This present work used the subcortical and cortical features of 278 subjects from the ADNI dataset to identify AD and sMRI. Multi-class classification is used for the experiment i.e., AD, EMCI, LMCI, HC. The proposed feature selection consists of Forward feature selection, Backward feature selection, and Combined PCA & RBM. Forward and backward feature selection methods use an iterative method starting being no features in the forward feature selection and backward feature selection with all features included in the technique. PCA is used to reduce the dimensions and RBM is used to select the best feature without interpreting the features. We have compared the three models with PCA to analysis. The following experiment shows that combined PCA &RBM, and backward feature selection give the best accuracy with respective classification model RF i.e., 88.65, 88.56% respectively.

Bayesian bi-level variable selection for genome-wide survival study

  • Eunjee Lee;Joseph G. Ibrahim;Hongtu Zhu
    • Genomics & Informatics
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    • 제21권3호
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    • pp.28.1-28.13
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    • 2023
  • Mild cognitive impairment (MCI) is a clinical syndrome characterized by the onset and evolution of cognitive impairments, often considered a transitional stage to Alzheimer's disease (AD). The genetic traits of MCI patients who experience a rapid progression to AD can enhance early diagnosis capabilities and facilitate drug discovery for AD. While a genome-wide association study (GWAS) is a standard tool for identifying single nucleotide polymorphisms (SNPs) related to a disease, it fails to detect SNPs with small effect sizes due to stringent control for multiple testing. Additionally, the method does not consider the group structures of SNPs, such as genes or linkage disequilibrium blocks, which can provide valuable insights into the genetic architecture. To address the limitations, we propose a Bayesian bi-level variable selection method that detects SNPs associated with time of conversion from MCI to AD. Our approach integrates group inclusion indicators into an accelerated failure time model to identify important SNP groups. Additionally, we employ data augmentation techniques to impute censored time values using a predictive posterior. We adapt Dirichlet-Laplace shrinkage priors to incorporate the group structure for SNP-level variable selection. In the simulation study, our method outperformed other competing methods regarding variable selection. The analysis of Alzheimer's Disease Neuroimaging Initiative (ADNI) data revealed several genes directly or indirectly related to AD, whereas a classical GWAS did not identify any significant SNPs.

Possible Health Effects of Caffeinated Coffee Consumption on Alzheimer's Disease and Cardiovascular Disease

  • You, Dong-Chul;Kim, Young-Soon;Ha, Ae-Wha;Lee, Yu-Na;Kim, Soo-Min;Kim, Chun-Heum;Lee, Seung-Ha;Choi, Dal-Woong;Lee, Jae-Min
    • Toxicological Research
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    • 제27권1호
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    • pp.7-10
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    • 2011
  • Coffee has been known to have both beneficial and harmful effects upon health. Coffee is one of the most widely consumed beverages, worldwide. Dementia/Alzheimer's disease (AD) and cardiovascular disease (CVD) are public health problems that are rapidly increasing in the aging population. Due to the high consumption of coffee, even small effects on an individual's health could have a large effect on public health. The aim of this review article is to provide an overview of previously published studies of coffee consumption on health. Herein, we focus on epidemiological and experimental findings to investigate whether coffee-drinking habits, and/or the quantity of coffee consumption, have any relationship to CVD, dementia/AD, and other chronic diseases. Although the underlying mechanisms are not fully understood, when comparing coffee drinkers with non-drinkers, moderate doses of caffeine showed protective effects against CVD and AD. We hypothesized that caffeine may be a novel therapy to treat CVD and dementia/AD.

Regulation of amyloid precursor protein processing by its KFERQ motif

  • Park, Ji-Seon;Kim, Dong-Hou;Yoon, Seung-Yong
    • BMB Reports
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    • 제49권6호
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    • pp.337-343
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    • 2016
  • Understanding of trafficking, processing, and degradation mechanisms of amyloid precursor protein (APP) is important because APP can be processed to produce β-amyloid (Aβ), a key pathogenic molecule in Alzheimer's disease (AD). Here, we found that APP contains KFERQ motif at its C-terminus, a consensus sequence for chaperone-mediated autophagy (CMA) or microautophagy which are another types of autophagy for degradation of pathogenic molecules in neurodegenerative diseases. Deletion of KFERQ in APP increased C-terminal fragments (CTFs) and secreted N-terminal fragments of APP and kept it away from lysosomes. KFERQ deletion did not abolish the interaction of APP or its cleaved products with heat shock cognate protein 70 (Hsc70), a protein necessary for CMA or microautophagy. These findings suggest that KFERQ motif is important for normal processing and degradation of APP to preclude the accumulation of APP-CTFs although it may not be important for CMA or microautophagy.

혈소판 라만 스펙트럼에서 특이값 분해에 의한 기저 합성을 통한 알츠하이머병 검출 (A screening of Alzheimer's disease using basis synthesis by singular value decomposition from Raman spectra of platelet)

  • 박아론;백성준
    • 한국산학기술학회논문지
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    • 제14권5호
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    • pp.2393-2399
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    • 2013
  • 본 논문에서는 특이값 분해(SVD: singular value decomposition)에 의한 기저 스펙트럼의 합성을 통해 혈소판 라만 스펙트럼에서 알츠하이머병(AD: Alzheimer's disease)을 검출하는 방법을 제안하였다. AD가 유도된 형질 전환 실험용 쥐의 혈소판에서 측정한 라만 스펙트럼은 가산 잡음과 배경 잡음의 제거와 정규화로 구성된 전처리 과정을 수행한다. 각 데이터 행렬의 열벡터는 AD와 정상(NR: normal)의 라만 스펙트럼으로 구성한다. 이 데이터 행렬을 SVD로 분해한 다음 각 행렬의 열벡터 12개를 AD와 NR의 기저 스펙트럼으로 결정한다. 분류 과정은 각 클래스의 기저 스펙트럼을 선형 합성한 스펙트럼과 분류 스펙트럼의 평균제곱근오차(root mean square error)가 최소인 클래스를 선택하는 것으로 완료된다. 278개의 혈소판 라만 스펙트럼을 사용한 실험에 따르면 제안한 방법의 평균 분류율은 약 97.6%로 주성분 분석(principle components analysis)으로 추출한 특징에 MLP(multi-layer perceptron)를 이용한 경우보다 약 6.1% 정도의 우수한 성능을 보였다. 이 결과에서 SVD에 의한 기저 스펙트럼이 혈소판 라만 스펙트럼에서 AD의 검출에 적합하게 사용될 수 있음을 확인하였다.

CT105로 유도된 신경모세포종 세포주에서 세심탕의 항치매 효과 (Effect on Alzheimer's Disease by Sesim-tang in CT105-overexpressed SK-N-SH Cell Lines)

  • 권형수;박치상;박창국
    • 대한한의학회지
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    • 제25권2호
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    • pp.138-150
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    • 2004
  • Objectives : Alzheimer's disease (AD) is a geriatric dementia that is widespread in old age. In the near future AD will be the biggest problem in public health service. Although a variety of oriental prescriptions, including Sesim-tang, have been traditionally utilized for the treatment of AD, their pharmacological effects and action mechanisms have not yet been fully elucidated. The present study investigated the effects of Sesim-tang on apoptotic cell death induced by CT105 (carboxy terminal 105 amino acid peptide fragment of APP) overexpression in SK-N-SH neuroblastoma cell lines. Methods: We studied the regenerative and inhibitory effects on Alzheimer's disease in CT105-induced SK-N-SH cell lines by Sesim-tang water extract. We examined for cell morphological pattern, DNA fragmentation, LDH activity assay, zymography assay, and immunohistochemistric analysis. Additionally, we investigated the association between the CT105 and neurite degeneration caused by CT105-induced apoptotic response in neurone cells. Results: Findings from our experiments have shown that Sesim-tang inhibits the synthesis or activities of CT105, which has neurotoxicities and apoptotic activities in the cell line. In addition, pretreatment with Sesim-tang ($>50\mu\textrm{g}/ml$ for 12 hours) partially prevented CT105-induced cytotoxicity in SK-N-SH cell lines. SK-N-SH cell lines overexpressed with CT105 exhibited remarkable apoptotic cell damage. Based on morphological observations by phase-contrast microscope and LDH activity measurements in the culture media, the CT105-induced cell death was significantly inhibited by Sesim-tang water extract. Sesim-tang was found to reduce the expression of APP and caspase-3 induced by CT105 in SK-N-SH cell lines and in rat hippocampus. Conclusions: As the result of this study, in the Sesim-tang group, apoptosis in the nervous system is inhibited, the repair against the degeneration of SK-N-SH cell lines by CT105 expression is promoted. Hence, Sesim-tang may be beneficial for the treatment of AD.

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