• 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.

• 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.

• 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 Aβ_1-40. 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.04a
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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.

• Genomics & Informatics
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• v.21 no.3
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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.

• Proceedings of the Korean Society of Computer Information Conference
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• 2021.07a
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• pp.305-307
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• 2021

Alzheimer's Disease (AD) is a cognitive disorder characterized by memory impairment that can be assessed at early stages based on administering clinical tests. However, the AD pathophysiological mechanism is still poorly understood due to the difficulty of distinguishing different levels of AD severity, even using a variety of brain modalities. Therefore, in this study, we present a hybrid EEG-fNIRS modalities to compensate for each other's weaknesses with the help of Machine Learning (ML) techniques for classifying four subject groups, including healthy controls (HC) and three distinguishable groups of AD levels. A concurrent EEF-fNIRS setup was used to record the data from 41 subjects during Oddball and 1-back tasks. We employed both a traditional neural network (NN) and a CNN-LSTM hybrid model for fNIRS and EEG, respectively. The final prediction was then obtained by using majority voting of those models. Classification results indicated that the hybrid EEG-fNIRS feature set achieved a higher accuracy (71.4%) by combining their complementary properties, compared to using EEG (67.9%) or fNIRS alone (68.9%). These findings demonstrate the potential of an EEG-fNIRS hybridization technique coupled with ML-based approaches for further AD studies.

• Journal of Applied Biological Chemistry
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• v.64 no.3
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• pp.299-307
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• 2021

Accumulation of amyloid beta (Aβ) and oxidative stress are the most common reason of Alzheimer's disease (AD). In the present study, we investigated the cognitive improvement effects of butanol (BuOH) fraction from Momordica charantia in Aβ_25-35-induced AD mouse model. To develop an AD mouse model, mice were received injection of Aβ_25-35, and then orally administered BuOH fraction from M. charantia at doses of 100 and 200 mg/kg/day during 14 days. In the T-maze and novel object recognition test, administration of BuOH fraction from M. charantia L. at doses of 100 and 200 mg/kg/day improved spatial ability and novel object recognition by increased explorations of novel route and new object. In addition, BuOH fraction of M. charantia-administered groups improved learning and memory abilities by decreased time to reach hidden platform in Morris water maze test. Oral administration of BuOH fraction from M. charantia significantly inhibited lipid peroxidation and nitric oxide levels in the brain, liver, and kidney compared with Aβ_25-35-induced control group. These results indicated that BuOH fraction of M. charantia improved Aβ_25-35-induced cognitive impairment by attenuating oxidative stress. Therefore, M. charantia could be useful for protection from Aβ_25-35-induced cognitive impairment.

• Journal of the Korea Academia-Industrial cooperation Society
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• v.20 no.5
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• pp.241-251
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• 2019

In the present study, we investigated the effect of microcurrent against cognitive impairment in Alzheimer's disease (AD) mice model. The cognitive impairment was induced by intracerebroventricularly injection of amyloid beta ($A{\beta}$) to ICR mouse brain, and four kinds of micorocurrent wave were applied to AD mice. We observed the improved cognitive ability in microcurrent-applied AD mice through novel object recognition test and Morris water maze test, compared to $A{\beta}$-injected control group. The contents of malondialdehyde generated by $A{\beta}$ in the brain were also reduced by microcurrent application. These effects of microcurrent were related to the modulation of $A{\beta}$ producing and brain-derived neurotrophic factor (BDNF). Microcurrent down-regulated ${\beta}$-secretase, presenilin 1, and presenilin 2 which were related amyloidogenic pathway, and up-regulated human brain-derived neurotrophic factor in the mice brain, especially Wave4 group [STEP FORM wave form (0, 1.5, 3, 5V), wave superposition]. These results suggest that microcurrent application could provide help for improvement learning and memory ability, at least partly.

• Journal of Oriental Neuropsychiatry
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• v.28 no.4
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• pp.391-399
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• 2017

Objectives: To determine the effects of Korean medicine on behavioral and psychological symptoms of dementia (BPSD) of an Alzheimer's disease (AD) patient. Methods: A 85-year old female patient diagnosed with AD was treated with herbal medicine formula Chungsimyeonja-tang (淸心蓮子湯), Woohwangchungsim-won (牛黃淸心元), and acupuncture. Korean version of Mini-mental State Examination (MMSE-K) scores were used at baseline and post treatment as outcome measures to evaluate clinical symptoms of the patient. Results: Improvements in MMSE-K post treatment scores were observed compare to those at baseline. BPSD were also alleviated. Such changes were visually noticeable. Conclusions: Herbal medicine and acupuncture treatment were effective in alleviating symptoms of AD. Further studies with a larger sample size and randomized clinical trials are needed to obtain more reliable and valid treatment outcomes.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.05a
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• pp.109-109
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• 2002

Alzheimer's disease (AD) is characterized by $\beta$-amyloid deposition and associated with loss of neuron cells in brain regions involved in learning and memory process. Many cases of early onset autosomal dominant inherited forms of AD are caused by mutation in the genes encoding presenilin-2 (PS-2).(omitted)