• Nuclear Medicine and Molecular Imaging
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• v.41 no.2
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• pp.112-117
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• 2007

Imaging distribution of ${\beta}-amyloid$ plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the ${\beta}-amyloid$ plaques includes using radiolabeled peptides which can be only applied for peripheral ${\beta}-amyloid$ plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging ${\beta}-amyloid$ plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for ${\beta}-amyloid$ imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for ${\beta}-amyloid$ imaging agent.

• 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.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.141.2-142
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• 2003

beta-Amyloid (A$\beta$) peptide is the major component of senile plaques and considered to have a causal role in the development and progression of Alzheimer's disease. There has been compelling evidence supporting that $A\beta$-induced cytotoxicity is mediated through oxidative and/or nitrosative stress. Recently, considerable attention has been focused on dietary manipulation of oxidative and/or nitrosative damage. L-Egrothioneine (EGT) is a low-molecular weight naturally occurring thiol compound of dietary origin which exists in milimolar concentrations in the brain, liver, kindney, erythrocytes, ocular tissues and in seminal fluids of mammals. (omitted)

• Journal of Yeungnam Medical Science
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• v.35 no.1
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• pp.1-6
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• 2018

Alzheimer's disease (AD) is a neurodegenerative disorder associated with extracellular plaques, composed of amyloid-beta ($A{\beta}$), in the brain. Although the precise mechanism underlying the neurotoxicity of $A{\beta}$ has not been established, $A{\beta}$ accumulation is the primary event in a cascade of events that lead to neurofibrillary degeneration and dementia. In particular, the $A{\beta}$ burden, as assessed by neuroimaging, has proved to be an excellent predictive biomarker. Positron emission tomography, using ligands such as $^{11}C$-labeled Pittsburgh Compound B or $^{18}F$-labeled tracers, such as $^{18}F$-florbetaben, $^{18}F$-florbetapir, and $^{18}F$-flutemetamol, which bind to $A{\beta}$ deposits in the brain, has been a valuable technique for visualizing and quantifying the deposition of $A{\beta}$ throughout the brain in living subjects. $A{\beta}$ imaging has very high sensitivity for detecting AD pathology. In addition, it can predict the progression from mild cognitive impairment to AD, and contribute to the development of disease-specific therapies.

• Proceedings of the Korean Society of Toxicology Conference
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• 2003.10b
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• pp.139-140
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• 2003

Inflammatory as well as oxidative tissue damage has been implicated in pathophysiology of Alzheimer's disease (AD), and non-steroidal anti-inflammatory drugs have been reported to have beneficial effects in the treatment or prevention of AD. In the present study, we investigated the effect of celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, on inflammatory cell death induced by beta-amyloid, a neurotoxic peptide associated with senile plaques formed in the brains of patients with AD.(omitted)

• Applied Microscopy
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• v.42 no.4
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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.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.327.2-327.2
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• 2002

Inflammatory as well as oxidative tissue damage has been associated with pathophysiology of Alzheimer's disease (AD), and nonsteroidal anti-inflammatory drugs have been shown to retard the progress of AD. In this study, we have investigated the molecular mechanisms underlying oxidative and inflammatory cell death induced by beta-amyloid (Abeta), a neurotoxic peptide associated with senile plaques formed in the brains of patients with AD, in cultured PC12 cells. (omitted)

• Biomedical Science Letters
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• v.25 no.1
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• pp.7-14
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• 2019

Alzheimer's disease (AD) is highly prevalent in dementia, with no specifically effective treatment having yet been discovered. Amyloid plaques are one of the key hallmarks of AD. Transgenic mouse models exhibiting Alzheimer's disease-like pathology have been widely used to study the pathophysiology of Alzheimer's disease. In this study, we showed an age-dependent correlation between cognitive function, pathological findings, and [F-18] Florbetaben (FBB) PET images. Nineteen transgenic mice (12 with AD, 7 with controls) were used for this study. We observed an increase in ${\beta}$-Amyloid deposition ($A{\beta}$) in brain tissue and [F-18] FBB amyloid PET imaging in the AD group. The [F-18] FBB data showed a mildly negative trend with cognitive function. Pathological findings were negatively correlated with cognitive functions. These finding suggests that amyloid beta deposition can be well-monitored with [F-18] FBB PET and a decline in cognitive function is related to the increase in amyloid plaque burden.

• Molecular & Cellular Toxicology
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• v.5 no.2
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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.

• Proceedings of the Korean Society of Toxicology Conference
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• 2002.11b
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• pp.191-191
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• 2002

Inflammatory as well as oxidative tissue damage has been associated with pathophysiology of Alzheimer's disease (AD), and nonsteroidal anti-inflammatory drugs have been shown to retard the progress of AD. In this study, we have investigated the molecular mechanisms underlying oxidative and inflammatory cell death induced by beta-amyloid (Abeta), a neurotoxic peptide associated with senile plaques formed in the brains of patients with AD, in cultured PC12 cells.(omitted)