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Diagnostic Tools for Alzheimer's Disease: A Narrative Review Based on Our Own Research Experience

  • So-Hee Park;Kyoung Ja Kwon;Min Young Kim;Jae-Hun Kim;Won-Jin Moon;Hui Jin Ryu;Jae Won Jang;Yeonsil Moon;K-ARPI
    • Dementia and Neurocognitive Disorders
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    • v.22 no.1
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    • pp.16-27
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    • 2023
  • Alzheimer's disease (AD), one of the most representative neurodegenerative diseases, has diverse neurobiological and pathophysiological mechanisms. Treatment strategies targeting a single mechanism have repeated faced failures because the mechanism of neuronal cell death is very complex that is not fully understood yet. Since complex mechanisms exist to explain AD, a variety of diagnostic biomarkers for diagnosing AD are required. Moreover, standardized evaluations for comprehensive diagnosis using neuropsychological, imaging, and laboratory tools are needed. In this review, we summarize the latest clinical, neuropsychological, imaging, and laboratory evaluations to diagnose patients with AD based on our own experience in conducting a prospective study.

Neuroprotective roles of pituitary adenylate cyclase-activating polypeptide in neurodegenerative diseases

  • Lee, Eun Hye;Seo, Su Ryeon
    • BMB Reports
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    • v.47 no.7
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    • pp.369-375
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    • 2014
  • Pituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic bioactive peptide that was first isolated from an ovine hypothalamus in 1989. PACAP belongs to the secretin/glucagon/vasoactive intestinal polypeptide (VIP) superfamily. PACAP is widely distributed in the central and peripheral nervous systems and acts as a neurotransmitter, neuromodulator, and neurotrophic factor via three major receptors (PAC1, VPAC1, and VPAC2). Recent studies have shown a neuroprotective role of PACAP using in vitro and in vivo models. In this review, we briefly summarize the current findings on the neurotrophic and neuroprotective effects of PACAP in different brain injury models, such as cerebral ischemia, Parkinson's disease (PD), and Alzheimer's disease (AD). This review will provide information for the future development of therapeutic strategies in treatment of these neurodegenerative diseases.

An effect of UDCA in production of IL -1$\beta$ and NO by Microglia in Rat.

  • Joo, Seong-Soo;Kang, Hee-Chul;Lee, Do-Ik
    • Proceedings of the PSK Conference
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    • 2003.04a
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    • pp.208.1-208.1
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    • 2003
  • In recent, growing aged people in coupled with the increased senile dementia, Alzheimer's disease, has been a social interests to be cleared out. Alzheimer Disease(AD), first reported by Alios Alzheimer (1864-1915) in 1907, is a neurodegenrative disease. Nothing exact cause of AD is available by now, but in clinical founding ${\beta}$-amyloid peptide(A${\beta}$) and microtubule associated protein($\tau$ protein) is to involved in the disease, and the most important feature in AD is Known to induce chronic inflammation to neuron cell. (omitted)

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Emerging evidence that ginseng components improve cognition in subjective memory impairment, mild cognitive impairment, and early Alzheimer's disease dementia

  • Rami Lee;Ji-Hun Kim;Won-Woo Kim;Sung-Hee Hwang;Sun-Hye Choi;Jong-Hoon Kim;Ik-Hyun Cho;Manho Kim;Seung-Yeol Nah
    • Journal of Ginseng Research
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    • v.48 no.3
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    • pp.245-252
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    • 2024
  • Ginseng is a traditional herbal medicine used for prevention and treatment of various diseases as a tonic. Recent scientific cohort studies on life prolongation with ginseng consumption support this record, as those who consumed ginseng for more than 5 years had reduced mortality and cognitive decline compared to those who did not. Clinical studies have also shown that acute or long-term intake of ginseng total extract improves acute working memory performance or cognitive function in healthy individuals and those with subjective memory impairment (SMI), mild cognitive impairment (MCI), or early Alzheimer's disease (AD) dementia who are taking AD medication(s). Ginseng contains various components ranging from classical ginsenosides and polysaccharides to more recently described gintonin. However, it is unclear which ginseng component(s) might be the main candidate that contribute to memory or cognitive improvements or prevent cognitive decline in older individuals. This review describes recent clinical contributors to ginseng components in clinical tests and introduces emerging evidence that ginseng components could be novel candidates for cognitive improvement in older individuals, as ginseng components improve SMI cognition and exhibits add-on effects when coadministered with early AD dementia drugs. The mechanism behind the beneficial effects of ginseng components and how it improves cognition are presented. Additionally, this review shows how ginseng components can contribute to SMI, MCI, or early AD dementia when used as a supplementary food and/or medicine, and proposes a novel combination therapy of current AD medicines with ginseng component(s).

Hippocampus Segmentation and Classification in Alzheimer's Disease and Mild Cognitive Impairment Applied on MR Images

  • Madusanka, Nuwan;Choi, Yu Yong;Choi, Kyu Yeong;Lee, Kun Ho;Choi, Heung-Kook
    • Journal of Korea Multimedia Society
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    • v.20 no.2
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    • pp.205-215
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    • 2017
  • The brain magnetic resonance images (MRI) is an important imaging biomarker in Alzheimer's disease (AD) as the cerebral atrophy has been shown to strongly associate with cognitive symptoms. The decrease of volume estimates in different structures of the medial temporal lobe related to memory correlates with the decline of cognitive functions in neurodegenerative diseases. During the past decades several methods have been developed for quantifying the disease related atrophy of hippocampus from MRI. Special effort has been dedicated to separate AD and mild cognitive impairment (MCI) related modifications from normal aging for the purpose of early detection and prediction. We trained a multi-class support vector machine (SVM) with probabilistic outputs on a sample (n = 58) of 20 normal controls (NC), 19 individuals with MCI, and 19 individuals with AD. The model was then applied to the cross-validation of same data set which no labels were known and the predictions. This study presents data on the association between MRI quantitative parameters of hippocampus and its quantitative structural changes examination use on the classification of the diseases.

No Evidence of Association of Interleukin 1A (-889) Genetic Polymorphism with Alzheimer's Disease in Koreans

  • Jhoo, Jin Hyeong;Park, Woong Yang;Kim, Ki Woong;Lee, Kwang Hyuk;Lee, Dong Young;Youn, Jong Chul;Suh, Young Ju;Seo, Jeong-Sun;Woo, Jong Inn
    • Genomics & Informatics
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    • v.2 no.2
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    • pp.81-85
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    • 2004
  • To examine whether the IL-1A (-889) polymorphism associates with a risk for Alzheimer's disease (AD) and acts interactively with the apolipoprotein (APOE) $\epsilon$4 in the development of AD, we performed genotype analyses of the IL-1A and the APOE of the 102 Korean AD patients and 200 Korean non-demented controls. We failed to detect a significant difference in genotypic and allelic frequencies of IL-1A between the AD group and control group. No overexpression of the IL-1A C/T genotype and IL-1A T allele was found when we analyzed the late-onset and early-onset patients, separately. There was no significant genetic interaction between IL-1A polymorphism and the APOE polymorphism. I n conclusion, the IL-1A polymorphism did not contribute to the development of AD independently or interactively with the APOE $\epsilon$4 allele in Koreans.

Local Region Spectral Analysis for Performance Enhancement of Dementia Classification (인지증 판별 성능 향상을 위한 스펙트럼 국부 영역 분석 방법)

  • Park, Jun-Qyu;Baek, Seong-Joon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.11
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    • pp.5150-5155
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    • 2011
  • Alzheimer's disease (AD) and vascular dementia (VD) are the most common dementia. In this paper, we proposed a region selection for classification of AD, VD and normal (NOR) based on micro-Raman spectra from platelet. The preprocessing step is a smoothing followed by background elimination to the original spectra. Then we applied the minmax method for normalization. After the inspection of the preprocessed spectra, we found that 725-777, 1504-1592 and 1632-1700 $cm^{-1}$ regions are the most discriminative features in AD, VD and NOR spectra. We applied the feature transformation using PCA (principal component analysis) and NMF (nonnegative matrix factorization). The classification result of MAP(maximum a posteriori probability) involving 327 spectra transformed features using proposed local region showed about 92.8 % true classification average rate.

Analysis of the mechanism of fibrauretine alleviating Alzheimer's disease based on transcriptomics and proteomics

  • Lu Han;Weijia Chen;Ying Zong;Yan Zhao;Jianming Li;Zhongmei He;Rui Du
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.4
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    • pp.361-377
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    • 2024
  • The dried rattan stem of the Fibraurea Recisa Pierre plant contains the active ingredient known as fibrauretine (FN). Although it greatly affects Alzheimer's disease (AD), the mechanism of their effects still remains unclear. Proteomics and transcriptomics analysis methods were used in this study to determine the mechanism of FN in the treatment of AD. AD model is used through bilateral hippocampal injection of Aβ1-40. After successful modeling, FN was given for 30 days. The results showed that FN could improve the cognitive dysfunction of AD model rats, reduce the expression of AE and P-Tau, increase the content of acetylcholine and reduce the activity of acetylcholinesterase. The Kyoto Encyclopedia of Genes and Genomes enriched differentially expressed genes and proteins are involved in signaling pathways including metabolic pathway, AD, pathway in cancer, PI3K-AKT signaling pathway, and cAMP signaling pathway. Transcriptomics and proteomics sequencing resulted in 19 differentially expressed genes and proteins. Finally, in contrast to the model group, after FN treatment, the protein expressions and genes associated with the PI3K-AKT pathway were significantly improved in RT-qPCR and Western blot and assays. This is consistent with the findings of transcriptomic and proteomic analyses. Our study found that, FN may improve some symptoms of AD model rats through PI3K-AKT signaling pathway.

Panax ginseng as an adjuvant treatment for Alzheimer's disease

  • Kim, Hyeon-Joong;Jung, Seok-Won;Kim, Seog-Young;Cho, Ik-Hyun;Kim, Hyoung-Chun;Rhim, Hyewhon;Kim, Manho;Nah, Seung-Yeol
    • Journal of Ginseng Research
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    • v.42 no.4
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    • pp.401-411
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    • 2018
  • Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer's disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in patients with AD, and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid ${\beta}$-protein ($A{\beta}$) formation by inhibiting ${\beta}$- and ${\gamma}$-secretase activity or by activating the nonamyloidogenic pathway, inhibit acetylcholinesterase activity and $A{\beta}$-induced neurotoxicity, and decrease $A{\beta}$-induced production of reactive oxygen species and neuro-inflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates $A{\beta}$-induced cholinergic deficits in AD models. Similarly, gintonin inhibits $A{\beta}$-induced neurotoxicity and activates the nonamyloidogenic pathway to reduce $A{\beta}$ formation and to increase acetylcholine and choline acetyltransferase expression in the brain through lysophosphatidic acid receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems and neurogenesis, thereby ameliorating learning and memory impairments. It also improves cognitive functions in patients with AD. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses research demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.

Penalized logistic regression using functional connectivity as covariates with an application to mild cognitive impairment

  • Jung, Jae-Hwan;Ji, Seong-Jin;Zhu, Hongtu;Ibrahim, Joseph G.;Fan, Yong;Lee, Eunjee
    • Communications for Statistical Applications and Methods
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    • v.27 no.6
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    • pp.603-624
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    • 2020
  • There is an emerging interest in brain functional connectivity (FC) based on functional Magnetic Resonance Imaging in Alzheimer's disease (AD) studies. The complex and high-dimensional structure of FC makes it challenging to explore the association between altered connectivity and AD susceptibility. We develop a pipeline to refine FC as proper covariates in a penalized logistic regression model and classify normal and AD susceptible groups. Three different quantification methods are proposed for FC refinement. One of the methods is dimension reduction based on common component analysis (CCA), which is employed to address the limitations of the other methods. We applied the proposed pipeline to the Alzheimer's Disease Neuroimaging Initiative (ADNI) data and deduced pathogenic FC biomarkers associated with AD susceptibility. The refined FC biomarkers were related to brain regions for cognition, stimuli processing, and sensorimotor skills. We also demonstrated that a model using CCA performed better than others in terms of classification performance and goodness-of-fit.