• Molecular & Cellular Toxicology
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• 제5권2호
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• pp.108-112
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• 2009

Alzheimer's disease(AD) is a neurodegenerative disorder characterized pathologically by senile plaques, neurofibrillary tangles, and synapse loss. Especially, extracellular beta-amyloid (Abeta) deposition is a major pathological hallmark of Alzheimer's disease (AD). In AD senile plaques, high level of iron and car-bonylated Abeta were detected. Iron has a Lewis acid property which can increase the electrophilicity of carbonyls, which may react catalytically with nucleophiles, such as amines. Hence, this study investigated whether or not iron could promote the carbonylation of amine with malondialdehyde (MDA) in the physiological condition. As the basic study, we examined that iron might promote the conjugation reaction between propylamine, monoamine molecule and MDA in the physiological condition. As the concentration of iron increased, the fluorescence intensity produced from the conjugation reaction increased in a dose-dependent manner. Instead of propylamine, we applied the same reaction condition to Abeta 1-40 peptide, one of major components founded in AD senile plaques for the conjugation reaction. As the result, the fluorescence intensity produced from the conjugation reaction between Abeta 1-40 peptide and MDA showed the similar trend to that of the reaction used with propylamine. This study suggests that iron can accelerate the conjugation reaction of MDA to Abeta 1-40 peptide and play an another important role in deterioration of AD brain.

• BMB Reports
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• 제54권6호
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• pp.295-304
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• 2021

Olfactory neuropathology is a cause of olfactory loss in Alzheimer's disease (AD). Olfactory dysfunction is also associated with memory and cognitive dysfunction and is an incidental finding of AD dementia. Here we review neuropathological research on the olfactory system in AD, considering both structural and functional evidence. Experimental and clinical findings identify olfactory dysfunction as an early indicator of AD. In keeping with this, amyloid-β production and neuroinflammation are related to underlying causes of impaired olfaction. Notably, physiological features of the spatial map in the olfactory system suggest the evidence of ongoing neurodegeneration. Our aim in this review is to examine olfactory pathology findings essential to identifying mechanisms of olfactory dysfunction in the development of AD in hopes of supporting investigations leading towards revealing potential diagnostic methods and causes of early pathogenesis in the olfactory system.

• Journal of Ginseng Research
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• 제47권4호
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• pp.506-514
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• 2023

Dementia has become one of the most important diseases threatening human health. Alzheimer's disease (AD) and vascular dementia (VaD) have the highest incidence rates among the types of dementia, but until now, therapeutic methods have been limited. Panax ginseng has been used in China for thousands of years to treat dementia, and modern medical studies have found that it contains multiple active components, such as ginsenosides, polysaccharides, amino acids, volatile oils and polyacetylenes, many of which have therapeutic effects in treating AD and VaD. Studies have found that ginsenosides have multitarget therapeutic effects in treating dementia, such as regulation of synaptic plasticity and the cholinergic system, inhibition of Aβ aggravation and tau hyperphosphorylation, anti-neuroinflammation, anti-oxidation effects and anti-apoptosis effects. Other active components of Panax ginseng, such as gintonin, oligosaccharides, polysaccharides and ginseng proteins, also have therapeutic effects on AD and VaD. The effectiveness of ginseng-containing Chinese medicine compounds has also been confirmed by clinical and basic investigations in treating AD and VaD. In this review, we summarized the potential therapeutic effects and related mechanisms of Panax ginseng in treating AD and VaD to provide some examples for further studies.

• 말소리와 음성과학
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• 제5권1호
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• pp.27-38
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• 2013

Healthcare providers in Korea are using conservative pharmacological treatment for Alzheimer's disease (AD) to delay the progress of the disease or to mitigate its behavioral and neurological symptoms. However, there is a growing need for interventions using practical non-pharmacologic treatment, as the effects of pharmacological treatments has faced limitations. This research provided a cognitive rehabilitation program to 3 AD patients and used a multiple baseline design across subjects to examine the effects. Performing reality orientation therapy (ROT) for 1 cycle (4 weeks) resulted in a slight increase in accuracy and responsiveness on an orientation task, mainly with patients with mild cases of AD. Also, in the sub-domain of the Korean-Mini Mental Status Examination performed to examine changes in cognitive ability, there were minimal changes in place orientation. In functional communication, however, there were no significant differences before and after the intervention. In conclusion, we found that ROT was an effective intervention for improving accuracy and responsiveness in the orientation of patients with mild cases of AD. In future studies, the effect of non-pharmacological interventions can be evaluated more reliably by examining the interaction effects of sample size, length of the intervention, outcome measurements, and pharmacological intervention.

• 생물정신의학
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• 제23권2호
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• pp.48-56
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• 2016

Alzheimer's disease (AD) is a neurodegenerative disorder in which neuronal loss causes cognitive decline and other neuropsychiatric problems. It can be diagnosed based on history, examination, and appropriate objective assessments, using standard criteria such as the Diagnostic and Statistical Manual of Mental Disorders or the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). Brain imaging and biomarkers are making progress in the differential diagnoses among the different disorders. The cholinesterase inhibitors, donepezil, rivastigmine and galantamine and N-methyl-D-aspartate receptors antagonist memantine are approved by the US Food and Drug Administration for AD. Recently some acetylcholinesterase inhibitors gained approval for the treatment of severe AD and became available in a higher dose formulation or a patch formulation. Optimal care in AD is multifactorial and it should include early diagnosis and multidisciplinary care with pharmacological and nonpharmacological interventions including exercise interventions, cognitive interventions and maintenance of social networks.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.1
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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)

• Animal cells and systems
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• 제5권2호
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• pp.139-143
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• 2001

Alzheimer's disease is the most common form of dementia and no cure is known so far. Extensive genetic works and in vitro experiments combined with clinical observations link amyloid $\beta$--protein (A$\beta$-) to the pathogenesis of Alzheimer's disease (AD). It was hypothesized that $A\beta$- becomes toxic when it adopts a fibrillar conformation. Recently, non-fibrillar form of $A\beta$- was observed and the potential role in the pathogenesis of AD became an interesting subject. In this study, the cytotoxicity of non-fibrillar $A\beta$- and fibrillar $A\beta$- was compared on oxidative stress, membrane damage, or nucleosome break down. Non-fibrillar $A\beta$- was not toxic in peripheral nervous system-derived cells but significantly toxic in central nervous system-derived cells while fibrillar $A\beta$- was non-selectively toxic in both cell culture. The neurotoxicity of non-fibrillar $A\beta$- was reproduced in semi-in vivo culture of mouse brain slice. In conclusion, non-fibrillar $A\beta$- could be more relevant to the selective neurodegeneration in Alzheimer's brains than fibrillar $A\beta$- and further research needs to be done for identification of the cause of AD.

• 한국약용작물학회:학술대회논문집
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• 한국약용작물학회 2011년도 추계학술발표회
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• pp.31-45
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• 2011

The amyloid ${\beta}$-peptide ($A{\beta}$), which originates from the proteolytic cleavage of amyloid precursor protein (APP), plays a central role in the pathogenesis of Alzheimer's disease (AD). Mounting evidence indicates that different species of $A{\beta}$, such as $A{\beta}$ oligomers and fibrils, may contribute to AD pathogenesis via distinct mechanisms at different stages of the disease. Importantly, elevation and accumulation of soluble $A{\beta}$ oligomers closely correlate with cognitive decline and/or disease progression in animal models of AD. In agreement with these studies, oligomers of $A{\beta}$ have been shown to directly affect synaptic plasticity, a neuronal process that is known to be essential for memory formation. Our previous studies showed that $A{\beta}$ induces the breakdown of phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2), a phospholipid that regulates key aspects of neuronal function. PI(4,5)P2 breakdown was found to be a key step toward synaptic and memory dysfunction in a mouse model of AD. To this end, we seek to identify small molecules that could elevate the levels of PI(4,5)P2 and subsequently block $A{\beta}$ oligomer-induced breakdown of PI(4,5)P2 and synaptic dysfunction.. We found that (20S)Rg3, an active triterpene glycoside from heat-processed ginseng, serves as an agonist for phosphatidylinositol 4-kinase IIalpha (PI4KIIalpha), which is a lipid kinase that mediates a rate-limiting step in PI(4,5)P2 synthesis. Consequently, (20S)Rg3 stimulates PI(4,5)P2 synthesis by directly stimulating the activity of PI4KIIalpha. Interestingly, treatment of a mouse model of AD with (20S)Rg3 leads to reversal of memory deficits. Our data suggest that the PI(4,5)P2-promoting effects of (20S)Rg3 may help mitigate the cognitive symptoms associated with AD.

• Applied Microscopy
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• 제42권4호
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• pp.179-185
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• 2012

Alzheimer's disease (AD) is a progressive neurodegenerative disorder. Neuropathological hallmarks of AD are amyloid plaques, dystrophic neurite, and alteration of subcellular organelles. However, the morpho-functional study of this degenerative process and ultimate neuronal death remains poorly elucidated. In this study, immunohistochemical and ultrastructural analyses were performed to clarify the abnormal morphological alterations caused by the progression of AD in APP/PSEN1 transgenic mice, express human amyloid precursor protein, as a model for AD. In transgenic AD mice brain, the accumulation of Amyloid ${\beta}$ plaques and well-developed dystrophic neurites containing anti-LC3 antibody-positive autophagosomes were detected in the hippocampus and cortex regions. We also found severe disruption of mitochondrial cristae using high-voltage electron microscopy and three-dimensional electron tomography (3D tomography). These results provide morpho-functional evidence on the alteration of subcellular organelles in AD and may help in the investigation of the pathogenesis of AD.

• KSII Transactions on Internet and Information Systems (TIIS)
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• 제17권11호
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• pp.2924-2944
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• 2023

Alzheimer's disease (AD) is a neurological condition that is recognized as one of the primary causes of memory loss. AD currently has no cure. Therefore, the need to develop an efficient model with high precision for timely detection of the disease is very essential. When AD is detected early, treatment would be most likely successful. The most often utilized indicators for AD identification are the Mini-mental state examination (MMSE), and the clinical dementia. However, the use of these indicators as ground truth marking could be imprecise for AD detection. Researchers have proposed several computer-aided frameworks and lately, the supervised model is mostly used. In this study, we propose a novel 3D Convolutional Neural Network Multilayer Perceptron (3D CNN-MLP) based model for AD classification. The model uses Attention Mechanism to automatically extract relevant features from Magnetic Resonance Images (MRI) to generate probability maps which serves as input for the MLP classifier. Three MRI scan categories were considered, thus AD dementia patients, Mild Cognitive Impairment patients (MCI), and Normal Control (NC) or healthy patients. The performance of the model is assessed by comparing basic CNN, VGG16, DenseNet models, and other state of the art works. The models were adjusted to fit the 3D images before the comparison was done. Our model exhibited excellent classification performance, with an accuracy of 91.27% for AD and NC, 80.85% for MCI and NC, and 87.34% for AD and MCI.