치매의 病理에 대한 東·西醫學的 考察

柳泳秀,姜亨源,李光揆,崔用德 대한동의병리학회 1999 동의생리병리학회지 Vol.13 No.1

전 세계적으로는 1700만에서 2500만명이 알츠하이머병 환자가 있고 실제로 85세이상의 인구중 약 50%가 알츠하이머병인 것으로 알려져 있다. 알츠하이머형 치매의 경우 腦에서 大腦皮質의 萎縮, 副交感神經과 다른 神經細胞의 退化, neurofibrillary tangles(신경원섬유농축제, NFTs)의 存在, senile plaques(노인반)의 蓄積과 같은 4가지 구조적변화가 나타나며 neurofibrillary tangles와 senile plaques는 알츠하이머형 치매의 지표로 인식되고 있다. 그러나 지금도 알츠하이머병에 대한 發病原因이 不分明하여 硏究를 계속 進行 중이다. 특히 腦의 構造에서 非正常的으로 발견되는 두 가지 構造인 neurofibrillary tangles와 senile plaques가 무엇이며, 이러한 구조가 어떻게 만들어졌는가를 중심으로 활발히 硏究가 이루어지고 있다. 이에 著者는 이미 腦 代表的인 退行性 疾患으로 알려진 알츠하이머형 치매에 나타난 病理的 所見과 最近 發表된 硏究를 中心으로 韓醫學的인 病因病機를 比較 分析하였다. 痴매의 老化와 遺傳的 要因이 韓醫學의 臟腑的으로는 腎虛와 밀접한 關係를 맺고, 베타-아밀로이드와 tau 단백질과 같은 뇌속의 비정상적인 plaque는 痰濁과 瘀血 등의 韓方的 病理産物과 유사한 의미를 가지므로 실제 임상에 있어서도 베타-아밀로이드와 tau 단백질을 除去하는 서양의학적인 原因除去 治療法과 韓醫學的인 腦와 五臟과 關係에서 補腎法과 祛痰化瘀法을 竝行한다면 보다 나은 효과가 있을 것으로 思料된다. Through study of eastern and western records of dementia, the result were obtained as follows ; 1. The chief expression and pathogenic change of alzheimer's disease, the typical degenerative disease of brain, is overall cerebrum atropy, cerebral ventricular enlargement, senile plaque and neurofillary tangles(NFTs) etc. 2. The etiology of dementia is genetic factors, immunologic factor, virus, toxic substance and cephalic trauma etc. Among the rest, the genetic factor is being studied vigorously. 3. The typical substance of expired dementia brain cell are β-amyloid and tau protein. The accumulation of β-amyloid is known as the cause of senile plaque and amyloid angiopathy. The neurofillary tangles are known as substance made through the process of hyperphosphate of tau, a protein of neuronal cell frame. 4. From the oriental medical point of view, the defficiency of the kidney, liver and heart is the basic internal cause of dementia DamTak(痰濁), Blood stasis(瘀血), Chiljung(七情), Fung(風) and Hua(火) are exterior cause factor. Among the rest, the defficiency of the kidney is the most cause factor. 5. From the oriental medical point of view, the aging and genetic factor of dementia have much connection with the defficiency of kidney. Abnormal plaques of the brain such similar to the estern pathogenic substance such as Domtak(痰濁) and Blood stasis(瘀血). Like this, as the result of the study about the pathogenic subsntce of dementia is being studied vigorously, to treat dementia, etiologic factor-β-amyloid, tau protein-removal therapy and the eastern Bushen(補腎) therapy and Qutanhuayu(祛痰化瘀) therapy is likely to help the better clinical application.

Iron Can Accelerate the Conjugation Reaction between Abeta 1-40 Peptide and MDA

Park, Yong-Hoon,Jung, Jai-Yun,Son, Il-Hong The Korean Society of Toxicogenomics and Toxicopro 2009 Molecular & cellular toxicology Vol.5 No.2

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.

부검으로 확진된 알쯔하이머병 1예 : An Autopsy Report

한설희,이건국,양기화,장순환 대한치매학회 2002 Dementia and Neurocognitive Disorders Vol.1 No.1

While the clinical diagnostic accuracy of probable Alzheimer′s disease (AD) is 87-96% with a diagnostic sensitivity/specificity of 0 81-0 87, the unequivocal diagnosis of AD rests on histopathological evidence at brain autopsy and/or biopsy We report here a 92-year-old woman whose clinical presentation suggested a far advanced Alzheimer′s disease Formal neuropsychological evaluations were not applicable due to severe cognitive impairments With a relatively good general physical condition she could walk with aid during her last days no focal neurological signs were noted on a detailed examination Brain MRI revealed a diffuse cortical atrophy with a marked reduction in the hippocampal volume The brain obtained weighted 780g The cerebral hemispheres examined after fixation disclosed moderately severe atrophy in prefrontal and temporal lobes on coronal section, the hippocampus was likewise severely atrophied the lateral ventricles were moderately dilated On microscope examination, there were numerous senile plaques and neurofibrillary tangles in the neocortices. hippocampus and amyglada, compatible with advanced Alzheimer′s disease In summary we report the first Korean autopsy-proven case with advanced Alzheimer′s disease.

Relationship between Different Brain Regions in Hierarchial Order of Neurofibrillary Tangles and Senile Plaques in Alzheimer Brain

Jeong, Jee-Hyang,Park, Kee-Duk,Choi, Kyoung-Gyu 대한치매학회 2003 Dementia and Neurocognitive Disorders Vol.2 No.1

Background:Neurodegenerative process in AD is characterized by progressive neuronal and synaptic loss with gliosis and formation of senile plaque and neurofibriollary tangles. Relationship between severity of NFTs and SPs has still intriguing aspect. Methods:Hierarchial rank order of NFT and SPs was done instead of absolute morphometric quantitation to find out severity of each pathologic changed in regions of frontal, temporal, hippocampus, amygdala, entorrhinal cortex, piriform cortex, basal nucleus of Meynert(BNM), substantia nigra and locus coeruleus. Also age and brain weight were analyzed to find out relationship to each region. Results:Weight of brain showed significant correlation with neuronal loss in frontal, temporal and BNM but it did not show any correlation with the neuronal loss in LC., SN and amygdala. In amygdala NFT were high in cortical and cortical transitional nuclei. SPs were heavily accumulated in basomedial,, cortical and cortical transitional nuclei. In hippocampus, entorrhinal cortex, H1 and subiculum of the hippocampus were the most consistent and severely affected regions. BNM did not show any correlation with laterobasal nucleus of amygdala which projects to BNM. SN, LC as well as BNM were interrelated in the severity of these changes. Nevertheless, these changes were not correlated with the brain weight. Conclusion:Different regional vulnerability even in a single area is demonstrated in an hierarchial order. But it is still a perpetuating question how these regional vulnerability occurs.

3D-QSAR of PET Agents for Imaging β-Amyloid in Alzheimer’s Disease

Mi Kyoung Kim,Il Han Choo,Hyo Sun Lee,Jong Inn Woo,Youhoon Chong* 대한화학회 2007 Bulletin of the Korean Chemical Society Vol.28 No.7

Alzheimer병의 신경병리학적 소견과 분자생물학적 연구동향

손윤경 啓明大學校 醫科大學 1997 계명의대학술지 Vol.16 No.3

대뇌피질의 신경퇴행성 병변중 가장 흔한 AD의 조직학적 진단 기준은 전형적 노인반과 신경섬유 농축체의 분포와 밀도 등으로 볼 수 있다. AD의 병리 기선은 규명되어 있지 않으나 아밀로이드의 형성과 조직내 축적이 가장 주목을 받고 있다. 그러나 아밀로이드의 축적만으로 치매 증상의 정도와 유의한 관계가 있을 것으로 생각되는 대뇌피질 전반에 걸친 신경섬유 농축체 등 신경세포 변성과 소실, 이에 수반된 신경접합부의 이상형성등의 기전을 다 설명할 수 없으며 이러한 분야들이 앞으로 해결해야 할 과제라 생각된다. Alzheimer's disease(AD) is the commonest form degenerative diseases of the cerebral cortex. The neuropathologically diagnostic criteria of AD are focused on the distrubution and numbers of senile plaques and neurofibrillary tangles. Its pathogenesis is not fully elucidated until now. It is clear that the amyloidogenesis and its pathogenic activity are presently the dominant hypotheses concerning the AD development. However, they are not enough in understanding the diffuse neuronal degeneration such as neurofibrillary tangles, synaptic disconnection and neuronal loss which are related to the clinial dementia syndrome.

Novel Indole Derivatives as Potential Imaging Agents for Alzheimer's Disease

Yu, Lihai,Scheunemann, Matthias,Deuther-Conrad, Winnie,Hiller, Achim,Fischer, Steffen,Sorger, Dietlind,Sabri, Osama,Jia, Hongmei,Steinbach, Jorg,Brust, Peter,Liu, Boli Korean Chemical Society 2010 Bulletin of the Korean Chemical Society Vol.31 No.1

Novel Indole Derivatives as Potential Imaging Agents for Alzheimer’s Disease

Lihai Yu,Matthias Scheunemann,Winnie Deuther-Conrad,Achim Hiller,Steffen Fischer,Dietlind Sorger,Osama Sabri,Hongmei Jia,Jörg Steinbach,Peter Brust,Boli Liu 대한화학회 2010 Bulletin of the Korean Chemical Society Vol.31 No.1

뇌 생검으로 진단된 알쯔하이머병 2예

김희성,서연림,홍경수,나덕렬 대한병리학회 1997 Journal of Pathology and Translational Medicine Vol.31 No.2

Aggregation of amyloid precursor proteins by aluminum in vitro

Chong, Young-Hae,Suh, Yoo-Hun 이화여자대학교 생명과학연구소 1996 생명과학연구논문집 Vol.7 No.-

The effect of various metal ions on aggregation of human recombinant amyloid precursor protein(APP)in vitro was investigated based on characterizations of altered migration on SDS-PAGE or immunoblots. Most biological metal ions tested had no significant effect on aggregation of APP. In contrast, AICI_3 in particular promoted aggregation of APP or APP-CT105 in a dose dependent manner. This effect of AICI_3 on APP mobility shift was prevented or reversed by the metal chelator, EDTA. Amorphous aggregates were observed in AICI_3 treated APP when examined by EM. These results suggest that aluminum may play a role in the pathogenesis of AD directly promoting aggregation of APP.