• BMB Reports
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• 제56권9호
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• pp.520-525
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• 2023

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by cognitive decline. Several recent studies demonstrated that impaired adult neurogenesis could contribute to AD-related cognitive impairment. Adult subventricular zone (SVZ) neurogenesis, which occurs in the lateral ventricles, plays a crucial role in structural plasticity and neural circuit maintenance. Alterations in adult SVZ neurogenesis are early events in AD, and impaired adult neurogenesis is influenced by the accumulation of intracellular Aβ. Although Aβ-overexpressing transgenic 5XFAD mice are an AD animal model well representative of Aβ-related pathologies in the brain, the characterization of altered adult SVZ neurogenesis following AD progression in 5XFAD mice has not been thoroughly examined. Therefore, we validated the characterization of adult SVZ neurogenesis changes with AD progression in 2-, 4-, 8-, and 11-monthold male 5XFAD mice. We first investigated the Aβ accumulation in the SVZ using the 4G8 antibody. We observed intracellular Aβ accumulation in the SVZ of 2-month-old 5XFAD mice. In addition, 5XFAD mice exhibited significantly increased Aβ deposition in the SVZ with age. Next, we performed a histological analysis to investigate changes in various phases of adult neurogenesis, such as quiescence, proliferation, and differentiation, in SVZ. Compared to age-matched wild-type (WT) mice, quiescent neural stem cells were reduced in 5XFAD mice from 2-11 months of age. Moreover, proliferative neural stem cells were decreased in 5XFAD mice from 2 to 8 months of age. Furthermore, differentiations of neuroblasts were diminished in 5XFAD mice from 2-11 months of age. Intriguingly, we found that adult SVZ neurogenesis was reduced with aging in healthy mice. Taken together, our results revealed that impairment of adult SVZ neurogenesis appears with aging or AD progression.

• 노인정신의학
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• 제16권1호
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• pp.17-23
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• 2012

The diagnosis of Alzheimer's disease (AD) is still obscure even to specialists. To improve the diagnostic accuracy, to find at-risk people as early as possible, to predict the efficacy or adverse reactions of pharmacotherapy on an individual basis, to attain more reliable results of clinical trials by recruiting better defined participants, to prove the disease-modifying ability of new candidate drugs, to establish prognosis-based therapeutic plans, and to do more, is now increasing the need for biomarkers for AD. Among AD-related biochemical markers, cerebrospinal beta-amyloid and tau have been paid the most attention since they are materials directly interfacing the brain interstitium and can be obtained through the lumbar puncture. Level of beta-amyloid is reduced whereas tau is increased in cerebrospinal fluid of AD patients relative to cognitively normal elderly people. Remarkably, such information has been found to help predict AD conversion of mild cognitive impairment. Despite inconsistent findings from previous studies, plasma beta-amyloid is thought to be increased before the disease onset, but show decreasing change as the disease progress. Regarding other peripheral biochemical markers, omics tools are being widely used not only to find useful biomarkers but also to generate novel hypotheses for AD pathogenesis and to lead new personalized future medicine.

• 성인간호학회지
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• 제28권4호
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• pp.367-377
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• 2016

Purpose: The purpose of this study was to explore the quality of life (QoL) in patients with Alzheimer's disease (AD) and their and caregivers and its influencing factors. Methods: A descriptive research design was used. 211 pairs of AD patients and their caregivers were recruited from a neurology outpatient clinic of S medical center in Seoul, Korea. Caregivers completed several structured questionnaires regarding AD patients' QoL as well as their QoL, patients' behavioral and psychological symptoms, patients' activities of daily living (ADL), social support, and quality of relationship between AD patients and caregivers. Cognitive status of AD patients was assessed by the researchers using Korean Mini-Mental State Examination. Results: The scores of QoL were 26.91 for AD patients and 85.62 for their caregivers. In the multiple regression, factors associated with AD patients' QoL were the quality of relationship (${\beta}$=.44), ADL (${\beta}$=-.33), patient's age (${\beta}$=.20), caregivers' QoL (${\beta}$=.20), and patient's gender (${\beta}$=.11). Factors associated with caregivers' QoL were the quality of relationship (${\beta}$=.34), relationship (${\beta}$=.32), patient's QoL (${\beta}$=.26), caregivers' gender (${\beta}$=.18), social support (${\beta}$=.12), and the level of caregivers' education (${\beta}$=.12). Conclusion: To improve the QoL in AD patients and their caregivers, strategies to promote their quality of relationship are needed.

• Biomolecules & Therapeutics
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• 제28권2호
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• pp.131-136
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• 2020

Hippocampal synaptic dysfunction is a hallmark of Alzheimer's disease (AD). Many agents regulating hippocampal synaptic plasticity show an ameliorative effect on AD pathology, making them potential candidates for AD therapy. In the present study, we investigated spinosin as a regulating agent of synaptic plasticity in AD. Spinosin attenuated amyloid β (Aβ)-induced long-term potentiation (LTP) impairment, and improved plasmin activity and protein level in the hippocampi of 5XFAD mice, a transgenic AD mouse model. Moreover, the effect of spinosin on hippocampal LTP in 5XFAD mice was prevented by 6-aminocaproic acid, a plasmin inhibitor. These results suggest that spinosin improves synaptic function in the AD hippocampus by regulating plasmin activity.

• 생물정신의학
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• 제30권1호
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• pp.24-30
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• 2023

Objectives Alzheimer's disease (AD) is the most common form of dementia in older adults, damaging the brain and resulting in impaired memory, thinking, and behavior. The identification of differentially expressed genes and related pathways among affected brain regions can provide more information on the mechanisms of AD. The aim of our study was to identify differentially expressed genes associated with AD and combined biomarkers among them to improve AD risk prediction accuracy. Methods Machine learning methods were used to compare the performance of the identified combined biomarkers. In this study, three publicly available gene expression datasets from the hippocampal brain region were used. Results We detected 31 significant common genes from two different microarray datasets using the limma package. Some of them belonged to 11 biological pathways. Combined biomarkers were identified in two microarray datasets and were evaluated in a different dataset. The performance of the predictive models using the combined biomarkers was superior to those of models using a single gene. When two genes were combined, the most predictive gene set in the evaluation dataset was ATR and PRKCB when linear discriminant analysis was applied. Conclusions Combined biomarkers showed good performance in predicting the risk of AD. The constructed predictive nomogram using combined biomarkers could easily be used by clinicians to identify high-risk individuals so that more efficient trials could be designed to reduce the incidence of AD.

• 대한치매학회지
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• 제17권4호
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• pp.156-162
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• 2018

Background and Purpose: Previous studies have reported conflicting results about the prevalence of seizures in Alzheimer's disease (AD). There are few epidemiological studies on this topic in Asia. Thus, the objective of this study was to examine demographic and clinical characteristics as well as incidence for seizures in AD patients compared to non-AD patients in a prospective, longitudinal, community-based cohort with a long follow-up. Methods: Data were collected from National Health Insurance Service-National Elderly Cohort (NHIS-elderly) Database to define patients with AD from 2004-2006 using Korean Classification Diseases codes G30 and F00. We performed a 1:5 case-control propensity score matching based on age, sex, and household income. We conducted Cox proportional hazards regression analysis to estimate the risk of epilepsy in AD patients. Results: In the cohort study, patients with AD had higher risk for epilepsy than those without AD, with hazard ratio of 2.773 (95% confidence interval [CI], 2.515-3.057). This study also showed that male gender and comorbidities such as hypertension, hyperlipidemia, diabetes, and chronic kidney disease increased the risk of developing epilepsy. Patients with AD had 1.527 (95% CI, 1.375-1.695) times higher mortality rate than those in the control group. Conclusions: AD patients have significantly higher risk of developing epilepsy than non-AD patients.

• 동의생리병리학회지
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• 제34권5호
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• pp.222-228
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• 2020

The purpose of this article was to investigate the current state of studies on clinical trials of acupuncture treatment for Alzheimer's disease using neuroimaging method. We searched for clinical trials of acupuncture treatment for Alzheimer's disease(AD) and mild cognitive impairment(MCI) using neuroimaging method in the MEDLINE (Pubmed) database on March 18, 2020. Once the online search was finished, studies were selected manually by the inclusion criteria. Finally, we analyzed the characteristics of selected articles and reviewed the neural substrates of acupuncture treatment in AD. Total ten studies were included in this study. The most frequently applied modality for AD was functional MRI. The most frequently selected acupoints for AD were KI3, LR3 and LI4. One of studies showed that acupuncture treatment could improve the symptoms of MCI. Through the analysis, we demonstrated that neuroimaging method could capture the neural substrates associated with AD. Moreover, acupuncture may induce differential response according to the disease status. Finally, real acupuncture could produce more extensive activation/deactivation than sham acupuncture. We hope that neuroimaging method can contribute to the clinical research of acupuncture treatment for AD through large-scale RCT and diverse imaging modality.

• 한국멀티미디어학회논문지
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• 제23권8호
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• pp.940-952
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• 2020

The Alzheimer's disease (AD) is a neurodegenerative disease commonly found in the elderly individuals. It is one of the most common forms of dementia; patients with AD suffer from a degradation of cognitive abilities over time. To correctly diagnose AD, compuated-aided system equipped with automatic classification algorithm is of great importance. In this paper, we propose a novel deep learning based classification algorithm that takes advantage of MRI biomarker images including brain areas of hippocampus and cerebrospinal fluid for the purpose of improving the AD classification performance. In particular, we develop a new approach that effectively applies MRI biomarker patch images as input to 3D Deep Convolution Neural Network. To integrate multiple classification results from multiple biomarker patch images, we proposed the effective confidence score fusion that combine classification scores generated from soft-max layer. Experimental results show that AD classification performance can be considerably enhanced by using our proposed approach. Compared to the conventional AD classification approach relying on entire MRI input, our proposed method can improve AD classification performance of up to 10.57% thanks to using biomarker patch images. Moreover, the proposed method can attain better or comparable AD classification performances, compared to state-of-the-art methods.

• Journal of Ginseng Research
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• 제40권1호
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• pp.9-17
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• 2016

Background: Alzheimer's disease (AD) is a progressive brain disease, for which there is no effective drug therapy at present. Ginsenoside Rg1 (G-Rg1) and G-Rg2 have been reported to alleviate memory deterioration. However, the mechanism of their anti-AD effect has not yet been clearly elucidated. Methods: Ultra performance liquid chromatography tandem MS (UPLC/MS)-based metabolomics was used to identify metabolites that are differentially expressed in the brains of AD mice with or without ginsenoside treatment. The cognitive function of mice and pathological changes in the brain were also assessed using the Morris water maze (MWM) and immunohistochemistry, respectively. Results: The impaired cognitive function and increased hippocampal $A{\beta}$ deposition in AD mice were ameliorated by G-Rg1 and G-Rg2. In addition, a total of 11 potential biomarkers that are associated with the metabolism of lysophosphatidylcholines (LPCs), hypoxanthine, and sphingolipids were identified in the brains of AD mice and their levels were partly restored after treatment with G-Rg1 and G-Rg2. G-Rg1 and G-Rg2 treatment influenced the levels of hypoxanthine, dihydrosphingosine, hexadecasphinganine, LPC C 16:0, and LPC C 18:0 in AD mice. Additionally, G-Rg1 treatment also influenced the levels of phytosphingosine, LPC C 13:0, LPC C 15:0, LPC C 18:1, and LPC C 18:3 in AD mice. Conclusion: These results indicate that the improvements in cognitive function and morphological changes produced by G-Rg1 and G-Rg2 treatment are caused by regulation of related brain metabolic pathways. This will extend our understanding of the mechanisms involved in the effects of G-Rg1 and G-Rg2 on AD.

• 한국발생생물학회지:발생과생식
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• 제21권4호
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• pp.417-424
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• 2017

Alzheimer's disease (AD) is neurodegenerative disease, characterized by the progressive decline of memory, cognitive functions, and changes in personality. The major pathological features in postmortem brains are neurofibrillary tangles and amyloid beta ($A{\beta}$) deposits. The majority of AD cases are sporadic and age-related. Although AD pathogenesis has not been established, aging and declining mitochondrial function has been associated. Mitochondrial dysfunction has been observed in AD patients' brains and AD mice models, and the mice with a genetic defect in mitochondrial complex I showed enhanced $A{\beta}$ level in vivo. To elucidate the role of mitochondrial complex I in AD, we used SH-SY5Y cells transfected with DNA constructs expressing human amyloid precursor protein (APP) or human Swedish APP mutant (APP-swe). The expression of APP-swe increased the level of $A{\beta}$ protein in comparison with control. When complex I was inhibited by rotenone, the increase of ROS level was remarkably higher in the cells overexpressing APP-swe compared to control. The number of dead cell was significantly increased in APP-swe-expressing cells by complex I inhibition. We suggest that complex I dysfunction accelerate amyloid toxicity and mitochondrial complex I dysfunction in aging may contribute to the pathogenesis of sporadic AD.