• Title/Summary/Keyword: Alzheimer′s disease (AD)

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MicroRNA super-resolution imaging in blood for Alzheimer's disease

  • Mirae Lee;Jiwon Woo;Sang Tae Kim;Minho Moon;Sang Yun Kim;Hanna Cho;Sujin Kim;Han-Kyeol Kim;Jeong-Yoon Park
    • BMB Reports
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    • v.56 no.3
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    • pp.190-195
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    • 2023
  • We propose a novel blood biomarker detection method that uses miRNA super-resolution imaging to enable the early diagnosis of Alzheimer's disease (AD). Here, we report a single-molecule detection method for visualizing disease-specific miRNA in tissue from an AD mice model, and peripheral blood mononuclear cells (PBMCs) from AD patients. Using optimized Magnified Analysis of Proteome (MAPs), we confirmed that five miRNAs contribute to neurodegenerative disease in the brain hippocampi of 5XFAD and wild-type mice. We also assessed PBMCs isolated from the whole blood of AD patients and a healthy control group, and subsequently analyzed those samples using miRNA super-resolution imaging. We detected more miR-200a-3p expression in the cornu ammonis 1 and dentate gyrus regions of 3 month-old 5XFAD mice than in wild-type mice. Additionally, miRNA super-resolution imaging of blood provides AD diagnosis platform for studying miRNA regulation inside cells at the single molecule level. Our results present a potential liquid biopsy method that could improve the diagnosis of early stage AD and other diseases.

Alzheimer's Disease and Apoptosis

  • Kim, Young-Hoon;Kim, Hye-Sun;Park, Cheol-Hyoung;Jeong, Sung-Jin;Kim, Young-Kyung;Kim, Sun-Hee;Lee, Sang-Kyeng;Suh, Yoo-Hun;Kim, Sung Su
    • Korean Journal of Biological Psychiatry
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    • v.5 no.1
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    • pp.66-70
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    • 1998
  • Apoptosis is a form of cell death in which the cells shrink and exhibit nuclear chromatin condensation and DNA fragmentation, and yet maintain membrane integrity. Many lines of evidence have shown that brain neurons are vulnerable to degeneration by apoptosis. Also it has been suggested that apoptosis is one of the mechanism contributing neuronal loss in Alzheimer's disease(AD), since the conditions in the disease($A{\beta}$ peptide, oxidative stress, low energy metabolism) are the inducers that activate apoptosis. Indeed some neurons in vulnerable regions of the AD brain show DNA damage, chromatin condensation, and apoptic bodies. Consistently, mutations in AD causative genes(Amyloid precursor protein, Presenilin-1 and Presenilin- 2) increase $A{\beta}$ $peptide_{1-42}(A{\beta}_{1-42})$ and sensitize neuronal cell to apoposis. However, several lines of evidence have shown that the location of neuronal loss and $A{\beta}$ peptide deposition is not correlated in AD brain and transgenic mice brain over-expressing $A{\beta}_{1-42}$. Taken together, these data may indicated that $A{\beta}$ peptide(and other causative factors of AD) can interact with other cellular insults or risk factors to exacerbate pathological mechansim of AD through apoptosis. Thus, this review discusses possible role and mechanism of apoptosis in AD.

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Combination Treatment with SIP-3 Herb Formula and Donepezil: An NGS Study in the Mouse Model of Alzheimer's Disease Induced by Amyloid-β (SIP-3 한약 처방 및 도네페질의 병용 치료: 아밀로이드 베타로 유도된 알츠하이머병 생쥐 모델에서의 NGS 연구)

  • Oh, Young-je;Song, Sue-jin;Liu, Quan Feng;Son, Tae-kwon;Kim, Geun-woo;Koo, Byung-soo
    • Journal of Oriental Neuropsychiatry
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    • v.30 no.4
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    • pp.327-340
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    • 2019
  • Objectives: Alzheimer's disease (AD) is a complex disease accompanied by slow impairment of memory and coordination leading to behavioral changes. To date, the only treatment option is to delay the progress of the disease. The purpose of this study was to investigate the synergistic effects of combination treatment with donepezil and three herbal extracts SIP-3 in the AD mouse model induced by amyloid-β (Aβ). Methods: We tested SIP-3 extracts for the cytotoxicity on Aβ-treated SH-SY5Y cells. Then the synergistic effects of SIP-3 and donepezil were evaluated in the AD mouse model using animal experiments and the next generation sequencing (NGS) study. Results: We found that co-treatment with SIP-3 extracts and donepezil increased the viability in Aβ-treated SH-SY5Y cells. The beneficial effects of the co-treatment were also observed in the Aβ-induced AD mouse model. The NGS study was performed to show that the co-treatment of SIP-3 and donepezil restored the disease phenotype closely to the normal level in the AD mouse model in terms of mRNA expression. However, the phenotypes were only partially restored. Conclusions: This study suggests that the combination treatment has a potential to be used for the treatment of AD. However, longer periods of treatment may be required.

Effects on Alzheimer's disease by Jimitang in CT105-overexpressed SK-N-SH cell lines (CT105로 유도된 신경모세포종 세포주에서 지미탕(指迷湯)의 항치매효과)

  • Kang, Sung-Jun;Park, Chang-Gook;Park, Chi-Sang
    • The Journal of Internal Korean Medicine
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    • v.25 no.3
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    • pp.482-491
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    • 2004
  • Alzheimer's disease(AD) is a geriatric dementia that is widespread in old age. In the near future AD may be the biggest problem in public health service. Although a variety of oriental therapies in the study of Jimitang have been traditionally utilized for the treatment of AD, their pharmacological effects and active mechanisms have not been fully elucidated. This study in an investigation of effects of Jimitang on apoptotic cell death induced by CT105 overexpression in SK-N-SH neuroblastoma cell lines. DNA fragmentation, neurite outgrowth assay and LDH activity assay were examined. The regeneratory and inhibitory effects on Alzheimer's disease in pCT105-induced neuroblastoma cell lines by Jimitang water extract were examined. Findings from these experiments have shown that Jimitang inhibits the synthesis or activities of CT105, which has neurotoxicities and apoptotic activities in cell lines. In addition, pretreatment of $Jimitang(>50\;{\mu}g/mL\;for\;12\;hours)$ partially prevented CT(105)-induced cytotoxicity in SK-N-SH cell lines, and were inhibited by pretreatment. $Jimitang(>50\;{\mu}g/mL\;for\;12\;hours)$ repaired CT(105)-induced neurite outgrowth when SK-N-SH cell lines were transfected with CT(105). Results of this study show that. in the Jimitang group, the apoptosis in the nervous system in inhibited, the repair against the degerneration of neuroblastoma cells by CT105 expression is promoted. In addition, Jimitang was found to inhibit DNA fragmentation induced by CT105 overexpression, and promote neurite outgrowth. These findings suggest that Jimitang is beneficial for the treatment of AD.

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Neurobiology of Alzheimer's Disease (알쯔하이머 질환의 신경생물학)

  • Chung, Young-Cho;Seo, Seung-Woo;Lee, Seung-Hwan
    • Korean Journal of Biological Psychiatry
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    • v.8 no.1
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    • pp.62-70
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    • 2001
  • Alzheimer's disease(AD) is associated with a characteristic neuropathology. The major hallmarks of AD are senile plaques (SPs) and neurofibrillary tangles(NFTs). ${\beta}$-amyloid protein($A{\beta}$) is derived from the proteolysis of amyloid precursor protein(APP) and then converted to SPs. Mature SPs produce cytotoxicity through direct toxic effects and activation of microglia and complement. NFTs are composed of paired helical filaments(PHFs) including abnormally phosphorylated form of the microtubule-associated protein(MAP) tau and increased tau level in cerebrospinal fluid may be observed in most AD. The aggregation of $A{\beta}$ and tau formation are thought to be a final common pathway of AD. Acetylcholine, dopamine, serotonin, GABA and their receptors are associated with AD. Especially, decreased nicotinic acetylcholine receptors(nAChRs) in AD are reported. Genetic lesions associated with AD are mutations in the structural genes for the APP located on chromosome 21, presenilin(PSN)1 located on chromosome 14 and PSN2 located on chromosome 1. Also, trisomy 21, Apo-E gene located on chromosome 19, PMF locus, low density lipoprotein receptor-related protein and ${\alpha}$-macroglobulin increase risk of AD. In this article, we will review about the neurobiology of AD and some newly developed research areas.

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A Convergent Approach to Gain a Better Understanding of Alzheimer's Disease: Stereoscopic Vision (융복합적 접근을 통한 알츠하이머형 치매의 이해 증진 : 양안 지각)

  • Kim, Nam-Gyoon;Lee, Ho-Won
    • Journal of the Korea Convergence Society
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    • v.10 no.5
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    • pp.103-110
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    • 2019
  • The present study investigated the effects of AD on stereoscopic vision. Sixty participants (20 AD patients, 20 mild cognitive impairment patients, 20 healthy elderly controls) participated in the study. Two cubes, one on the left and the other on the right of the center of the monitor, appeared at varying distances from the observer with their relative distances controlled in two disparity conditions (absolute vs relative disparity) combined with two disparity directions (crossed vs uncrossed disparity). Participants identified the object that appeared closer to them. Results demonstrated comparable performance with all three groups performing accurately, suggesting that the effect of AD on stereopsis is negligible. Discussion focused on brain pathology affected by AD involving high level visual processing.

Function and dysfunction of leucine-rich repeat kinase 2 (LRRK2): Parkinson's disease and beyond

  • Bae, Jae Ryul;Lee, Byoung Dae
    • BMB Reports
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    • v.48 no.5
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    • pp.243-248
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    • 2015
  • Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). As such, functions and dysfunctions of LRRK2 in PD have been the subject of extensive investigation. In addition to PD, increasing evidence is suggesting that LRRK2 is associated with a wide range of diseases. Genome-wide association studies have implicated LRRK2 in Crohn's disease (CD) and leprosy, and the carriers with pathogenic mutations of LRRK2 show increased risk to develop particular types of cancer. LRRK2 mutations are rarely found in Alzheimer's disease (AD), but LRRK2 might play a part in tauopathies. The association of LRRK2 with the pathogenesis of apparently unrelated diseases remains enigmatic, but it might be related to the yet unknown diverse functions of LRRK2. Here, we reviewed current knowledge on the link between LRRK2 and several diseases, including PD, AD, CD, leprosy, and cancer, and discussed the possibility of targeting LRRK2 in such diseases. [BMB Reports 2015; 48(5): 243-248]

Cognitive improvement by ginseng in Alzheimer's disease

  • Lee, Soon-Tae;Chu, Kon;Kim, Jeong-Min;Park, Hyun-Jeong;Kim, Man-Ho
    • Journal of Ginseng Research
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    • v.31 no.1
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    • pp.51-53
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    • 2007
  • Ginseng shows protective and trophic effects in neurodegenerative diseases in experimental models, and showed cognitive improvement in normal population. To investigate the efficacy of ginseng in patients with Alzheimer's disease, patients, who met NINDS-ADRDA criteria for AD were studied Subjects were randomly assigned to ginseng group and control group, and ginseng group was treated with Korean white ginseng powder (4.5 g/day) for 12 weeks. Efficacy variables included changes in mini-mental status exam (MMSE) and cognitive subscales of Alzheimer's disease assessment scale (ADAS-cog) at 4 weeks and 12 weeks. Baseline MMSE and ADAS scores showed no difference between the two groups. Results showed that ginseng improved ADAS-cog compared to the control group at 12 weeks (p<0.05). MMSE was also increased by ginseng treatment compared to the control at 12 weeks (p<0.01). This study suggests the symptomatic efficacy of ginseng in patients with Alzheimer's disease.

A Method of Feature Extraction on Micro-Raman Spectra for Classification of Neuro-degenerative Disorders (마이크로 라만 스펙트럼에서 퇴행성 뇌신경질환 분류를 위한 특징 추출 방법 연구)

  • Park, Aa-Ron;Baek, Sung-June
    • Journal of the Institute of Electronics Engineers of Korea SC
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    • v.48 no.2
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    • pp.80-85
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    • 2011
  • Alzheimer's disease and Parkinson's disease are the most common neurodegenerative disorders. In this paper, we proposed a feature extraction method for classification of AD and PD based on micro-Raman spectra from platelet. The first step of the preprocessing is a simple smoothing followed by background elimination to the original spectra to make it easy to measure the intensity of the peaks. The last step of the preprocessing was peak alignment with the reference peak. After the inspection of the preprocessed spectra, we found that proportion of two peak intensity at 743 and $757cm^{-1}$ and peak intensity at 1248 and $1448cm^{-1}$ are the most discriminative features. Then we apply mapstd method for normalization. The method returned data with means to 0 and deviation to 1. With these three features, the classification result involving 263 spectra showed about 95.8% true classification in case of MAP(maximum a posteriori probability).

ApoE Allele Test in Korean with Hair Root DNA (모근 DNA를 이용한 한국인의 ApoE 유전자형 검사)

  • Kim, Chong-Ho;Jung, Mi-Ra;Park, Sang-Ho
    • Korean Journal of Clinical Laboratory Science
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    • v.38 no.3
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    • pp.179-183
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    • 2006
  • Alzheimer's disease (AD) is characterised neuropathologically by the accumulation of neuritic plaques and neurofibrillary tangles as well as by cerebrovascular amyloid deposition and neuronal cell loss. Current advances have shown the apolipoproteinE-epsilon 4 (ApoE4) allele to be highly associated with late-onset familial and sporadic Alzheimer's disease (AD) in Western populations. The association of ApoE allele frequencies and dementia remains unknown in populations from many countries. We recently initiated a project to examine ApoE frequencies in non-demented healthy Koreans. Genomic DNA in hair root from a thousand persons was collected and ApoE gene type was investigated with the methods of polymerase chain reaction (PCR) and restriction fragment length polymorphism. A group of a thousand non-demented Koreans over the age of 40 years were found to be positive in 15.7% of the cases for ApoE4. AD and ApoE4 were closely related. ApoE epsilon 4 was a dangerous factor of AD and ApoE 4 allele made a contribution to the heterogenicity of AD.

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