• Journal of Life Science
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• v.17 no.1 s.81
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• pp.18-23
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• 2007

Fe65, a neuron-specific adaptor protein, has two phosphotyrosine binding (PTB) domains. The second PTB (PTB2) domain interacts with intracellular domain fragment (AICD) of amyloid beta precursor protein (APP). Recent studies suggested that tile complex is composed of AICD and Fe65 transactivates genes that are responsible for neuronal cell death in Alzheimer's disease (AD). Therefore, a compound inhibiting the interaction between Fe65 and AICD can be a drug candidate to treat AD. However, it remains unclear how Fe65 recognizes AICD at a molecular level. Here, we report high-level production of the PTB2 domain of Fe65 in the baculovirus system. We found that the baculovirus system is an efficient method to obtain the Fe65 PTB2 domain, compared with the bacterial and mammalian expression systems. The purified recombinant protein was used for crystallization to determine its crystal structure helping to understand the molecular mechanism of Fe65-dependent signaling and to design its inhibitors.

• Journal of Korean geriatric psychiatry
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• v.16 no.1
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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.

• Journal of the Korean Society of Radiology
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• v.83 no.3
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• pp.486-507
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• 2022

Cerebral small vessel disease (CSVD) includes vascular lesions detected on brain MRI, such as white matter hyperintensities, lacunar infarctions, microbleeds, or enlarged perivascular spaces. There is accumulating evidence that vascular changes may play an important role in development of Alzheimer's disease (AD), and CSVD lesions detected on brain MRI were reported to be associated with β-amyloid and tau proteins accumulation. As the vascular contribution has therapeutic potential, it is important to understand the association of CSVD with AD and AD biomarkers. This review begins with a brief introduction of AD and AD biomarkers, explains the association between AD and vascular changes, and then details the pathogenesis and MR imaging findings of CSVD. Afterwards, we discuss the association of CSVD with AD and AD biomarkers.

• Sleep Medicine and Psychophysiology
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• v.28 no.2
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• pp.78-85
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• 2021

Objectives: When elderly patients show depressive symptoms, discrimination between depressive disorder and prodromal phase of Alzheimer's disease is important. We tested whether a quantitative electroencephalogram (qEEG) marker was associated with cerebral amyloid-β (Aβ) deposition in older adults with depression. Methods: Non-demented older individuals (≥ 55years) diagnosed with depression were included in the analyses (n = 63; 76.2% female; mean age ± standard deviation 73.7 ± 6.87 years). The participants were divided into Aβ+ (n = 32) and Aβ- (n = 31) groups based on amyloid PET assessment. EEG was recorded during the 7min eye-closed (EC) phase and 3min eye-open (EO) phase, and all EEG data were analyzed using Fourier transform spectral analysis. We tested interaction effects among Aβ positivity, condition (EC vs. EO), laterality (left, midline, or right), and polarity (frontal, central, or posterior) for EEG alpha band power. Then, the EC-to-EO alpha reactivity index (ARI) was examined as a neurophysiological marker for predicting Aβ+ in depressed older adults. Results: The mean power spectral density of the alpha band in EO phase showed a significant difference between the Aβ+ and Aβ- groups (F = 6.258, p = 0.015). A significant 3-way interaction was observed among Aβ positivity, condition, and laterality on alpha-band power after adjusting for age, sex, educational years, global cognitive function, medication use, and white matter hyperintensities on MRI (F = 3.720, p = 0.030). However, post-hoc analyses showed no significant difference in ARI according to Aβ status in any regions of interest. Conclusion: Among older adults with depression, increased power in EO phase alpha band was associated with Aβ positivity. However, EC-to-EO ARI was not confirmed as a predictor for Aβ+ in depressed older individuals. Future studies with larger samples are needed to confirm our results.

• Journal of Life Science
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• v.18 no.6
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• pp.796-803
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• 2008

Mutations in the APP gene lead to enhanced cleavage by ${\beta}-$ and ${\gamma}-secretase$, and increased $A{\beta}$ formation, which are closely associated with Alzheimer's disease (AD)-like neuropathological changes. Recent studies have shown that exercise training can ameliorate pathogenic phenotypes ($A{\beta}-42$, BDNF, GLUT-1 and HSP70) in experimental models of Alzheimer's disease. Here, we have used NSE/APPsw transgenic mice to investigate directly whether exercise training ameliorates pathogenic phenotypes within Alzheimer's brains. Sixteen weeks of exercise training resulted in a reduction of $A{\beta}-42$ peptides and also facilitated improvement of cognitive function. Furthermore, GLUT -1 and BDNF proteins produced by exercise training may protect brain neurons by inducing the concomitant expression of genes that encode proteins (HSP-70) which suppress stress induced neuron cell damages from APPsw transgenic mice. Thus, the improved cognitive function by exercise training may be mechanistically linked to a reduction of $A{\beta}-42$ peptides, possibly via activation of BDNF, GLUT-1, and HSP-70 proteins. On the basis of the evidences presented in this study, exercise training may represent a practical therapeutic management strategy for human subjects suffering from Alzheimer's disease.

• KIPS Transactions on Software and Data Engineering
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• v.3 no.10
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• pp.421-428
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• 2014

Like Alzheimer's disease, Parkinson's Disease(PD) is one of the most common neurodegenerative brain disorders. PD results from the deterioration of dopaminergic neurons in the brain region called the substantia nigra. Currently there is no cure for PD, but diagnosing in its early stage is important to provide treatments for relieving the symptoms and maintaining quality of life. Unlike many diagnosis methods of PD which use a single biomarker, we developed a diagnosis method that uses both biochemical biomarkers and imaging biomarkers. Our method uses ${\alpha}$-synuclein protein levels in the cerebrospinal fluid and diffusion tensor images(DTI). It achieved an accuracy over 91.3% in the 10-fold cross validation, and the best accuracy of 72% in an independent testing, which suggests a possibility for early detection of PD. We also analyzed the characteristics of the brain fiber pathways of Parkinson's disease patients and normal elderly people.

• Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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• 2010.06a
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• pp.219-219
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• 2010

In a past, the method in which it used the fluorescent material or it analyzes a gene was used in order to detect the Alzheimer's disease. However, in this paper, the magnetic bead is used in order to detect the Alzheimer's disease. The 'magnetic bead used in this paper is able to make the amyloid-beta and the selective binding known as cause of the Alzheimer's disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.18 no.1
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• pp.53-57
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• 2004

In order to evaluate the neuroprotective effects of Kamisinsunbulo-dan(KSM), the cytotoxicity of amyloid β and the recovering effect of KSM were checked at first. Then the viability of C6 cells was tested in comparison with each concentration of KSM. The cytotoxicity of amyloid β(31-35) showed from 5 μM higher to 100 μM. And the recovering effect by KSM showed significantly at 100㎍/㎖. concentration. And the cell viability was shown significantly over 200 ㎍/㎖ of KSM. This is thought that the viability has some relation to length of culturing duration, 6 to 12 hrs. Lastly in the western blotting of APP, the amount of low molecule's APP was decreased. So the APP form ratio(APPr) changed to increase, and it meant that KSM can be used to lower the toxic APP, and can be a candidate for Alzheimer's disease.

• Proceedings of the Korean Information Science Society Conference
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• 2011.06c
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• pp.377-378
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• 2011

본 논문은 뇌기능 연구에 크게 기여하는 기능적 자기공명영상을 효과적으로 분석하기 위한 유효 연결성(Effective Connectivity, EC)을 이용한 대규모 네트워크(Large-Scale Network, LSN) 분석(LSN-EC)을 제안한다. 유효 연결성은 뇌영역간의 시공간적 인과관계를 표현한 연결성이며, 뇌의 기능적 연결성 및 구조탐색 사용된다. LSN-EC는 뇌영역간의 EC를 표현하고 그룹간의 차이분석을 통하여 뇌질환 분석 및 진단 연구로의 응용이 가능하다. 실험결과에서 알츠하이머병과 관련이 높다고 알려진 후대상피질(Posterior Cingulate Cortex)과 해마(Hippocampus)가 포함된 변연엽(Limbic Lobe), 기저핵 및 시상(Basal Ganglion and Thalamus) 주변 영역에서 감소된 EC를 확인하였다.

• Proceedings of the KIEE Conference
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• 2003.07d
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• pp.2804-2806
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• 2003

생체신호는 생리학이나 해부학에서 주로 다루어졌으나, 최근 컴퓨터 시스템의 발전으로 공학적인 접근이 활발히 진행되고 있다. 특히 뇌의 정보를 보여주는 EEG(Electroencephalogram) 신호의 각 주파수 대역 별 에너지 분석은 의학분야에서도 매우 큰 비중을 두고 있다. 특정 뇌신경 관련질환이 갖는 대역별 주파수 특징과 Spike등을 분석하는 것은 치료와 예방에 아주 좋은 방법의 하나가 될 수 있다. 본 논문에서는 신호처리에서 높은 효율을 보이는 Wavelet Transform을 이용하여 알츠하이머병의 EEG 신호를 분석하였다.