Recent advances in Alzheimer’s disease pathogenesis and therapeutics from an immune perspective

Nguyen Thai-Duong,Dang Loi Nguyen,Jang Jung-Hee,박소연 한국약제학회 2023 Journal of Pharmaceutical Investigation Vol.53 No.5

Background The prevalence of Alzheimer’s disease, the most common type of dementia, is continuously increasing. Many recent reports have indicated that immune-related mechanisms play a vital role in Alzheimer’s disease pathogenesis, such that the imbalance between the immune response and central nervous system leads to neuroinflammation. Area covered The inflammatory response in Alzheimer’s disease is a “double-edged sword”. Neuroinflammation protects neuronal cells in the initial stages of Alzheimer’s disease, while sustained inflammation promotes neurodegeneration. Alterations in the peripheral immune system, such as increased inflammation, lead to the activation of the central immune response, which in turn causes neuroinflammation and neuronal damage. Additionally, an imbalance between pro- and anti-inflammatory cytokines, which are secreted by the central and peripheral immune systems, induces complex immune responses and contributes to Alzheimer’s disease pathogenesis. In this review, we aimed to summarize our current knowledge of the role of the immune system in Alzheimer’s disease pathology. We performed an in-depth investigation on the contribution of each immune system component to Alzheimer’s disease progression at different disease stages. More importantly, we discuss novel immune-related therapeutic strategies for Alzheimer’s disease treatment currently being investigated via clinical trials. Expert opinion The scrutinized observations of immune responses in different brain regions at various stages of Alzheimer’s disease might help identify potential treatment strategies for Alzheimer’s disease. The modulation of immune components in the brain by targeting cytokines and other factors, which compromise immune response and neuroinflammation, is recommended as a promising alternative for Alzheimer’s disease treatment. Clinical trials are currently investigating the efficacies of numerous vaccines and monoclonal antibodies targeting amyloid beta peptide and tau protein for Alzheimer’s disease treatment. Moreover, aducanumab and lecanemab were approved by the Food and Drug Administration as monoclonal antibody-based drugs for Alzheimer’s disease treatment in 2021 and 2023, respectively. However, these drugs are effective only against mild symptoms due to the irreversible neuronal damage found in patients with Alzheimer’s disease progression. In addition, side effects including amyloid-related imaging abnormalities (such as vasogenic edema, microhemorrhages, and hemosiderosis) were reported in patients undergoing Alzheimer’s disease treatment using monoclonal antibodies. Thus, the future development of therapeutic agents for Alzheimer’s disease requires more sophisticated and multi-plunged approaches considering various biomarkers and immune landscapes characterizing the different stages of Alzheimer’s disease.

알쯔하이머 질환의 신경신호전달계 이상소견

김영훈(Young-Hoon Kim),이상경(Sang-Kyeong Lee),김성수(Sung-Su Kim) 대한생물치료정신의학회 1997 생물치료정신의학 Vol.3 No.2

There are accumulating evidences that aging is regulated by different genes through several lines of biochemical processes simultaneously or independently. Aging of brain is accompanied with changes of several neurotransmitter systems. Most of all, abnormalities in the cholinergic system are remarkable. There are reductions in the number of neurons of Meynert's basal nucleus and activities of choline acetyltransferase in some areas of brain. Although reductions in other neurotransmitter systems such as dopaminergic, serotonergic and GABAergic system are also investigated, their involvement in the process of aging is still not throughly evaluated. However the brain levels of some of neuropeptides are decreased or increased, changes of them are less remakable than those of classical neurotransmitters. It is also suggested that functional abnormalities of G-protein and dysregulations of intracellular free calcium mobility are involved in the process of aging. Alzheimer's disease is a heterogenous disorder. Mutations of APP gene on chromosome 21, gene encoding preseinlin 1 on chromosome 14 and gene encoding presenilin 2 on chromosome 1 are thought to be causative factors in familial type of early-onset Alzheimer's disease(familial EOAD). There are several theories about the pathophysiology of Alzheimer's disease : cholinergic theory, β-amyloid protein theory, excitotoxicity theory and etc. Reductions in the cholinergic system are most remakable and consistently reported among several neurotransmitter abnormalities in Alzheimer's disease. Reduction in the activity of choline acetyltransferase is related to the impairment of cognitive functions in patients with Alzheimer's disease. Abnormalities in other neurotransmitter systems are also noticed, but the significance of those in the pathogenesis of Alzheimer's disease is not clear. In cases of neuropeptides, reduction in levels of somatostatin in some of brain areas involved in Alzheimer's disease is consistently reported in most of studies. Studies which investigated the nature of neurotransmitter receptors in Alzheimer's disease had several methodological limitations and were very scanty in amout. It is known that there are selective reductions of M2 muscarinic receptor and reductions in nicotinic receptors in general. Studies about other neurotansmitter receptors such as catecholaminergic, serotonergic and GABAergic receptors showed mixed and inconsistent results. Because the phenomenon of longterm potentiation regulated by NMDA receptor is regarded as a important model of memory processing and endogenous excitotoxic molecules binds to excitatory amino acid(EAA) receptors such as kainate receptors, further investigations about EAA receptors in Alzheimer's disease should be needed. Biological markers in Alzheimer's disease can be subdivided into cerebrospinal markers, peripheral markers and the findings obtained in brain imaging studies. The most remarkable is the reduction in levels of CSF somatostatin which is consistent with the findings in postmortem studies. The activity of platelet monoamine oxidase(MAO) is elevated in Alzheimer's disease, but that is also found in normal aging. To search the functional aspects of brain in patients with Alzheimer's disease using brain imaging techniques will be promising in the future. The finding of metabolic reduction in parietal cortex in positron emission tomography(PET)-scan is expected to have a role as a potent biological marker in early stage of Alzheimer's disease. The final goal of these researches is to ameliorate sufferings of the patients with Alzheimer's disease. At present, cholinergic therapy is the most expanding. it is more needed to define the exact nature of cholinergic abnormalities in Alzheimer's disease to reach easily the goals of pharmacological approaches. 노화는 여러 유전자들에 의해 조절되는 동시 진행적인 혹은 종속적인 일련의 생화학적 과정에 의해 진행된다는 근거가 있다. 뇌의 노화는 많은 신경전달계의 변화를 유발한다. 특히 콜린계 장애가 가장 현저하다. Meynert’s basal nucleus의 신경세포가 소실되고, choline acetyl transferase의 활성도가 감소한다. 도파민계, 세로토닌계,GABA계 등 대부분의 신경전달계의 저하가 알려져 있지만, 이들의 노화에의 원인적 기여에 대한 역할은 확실치 않다. 신경펲타이드계는 일부 저하되고 일부는 증가하나, 이들의 변화는 전형적 신경전달계의 변화에 비해 미미하다고 생각된다. 그 외 G 단백질의 기능 장애 및 세포내 유리 칼슘 이온의 조절 기능의 장애도 노화와 관련된 것으로 생각된다. 알쯔하이머 질환은 유전성 질환이다. 염색체 21번의 APP 유전자 돌연변이와 염색체 14번, 1번의 presenilin 1, 2 유전자 돌연변이가 특히 조기발병 알쯔하이머 질환과 관련이 있다. 현재 알쯔하이머 질환의 병인에 대해 cholinergic theory, β-amyloid protein theory, excitotoxicity theory 등 여러 가설이 있다. 알쯔하이머 질환의 신경전달계 장애로 가장 일관성 있게 보고된 것은 역시 콜린계 장애이다. 특히 choline acetyltransferase의 활성도 감소는 이 질환의 인지기능 저하소견과 상관성이 있다. 기타 신경전달계의 장애도 발견되나, 알쯔하이머 병인에의 기여 여부는 확실치 않다. 신경?타이드들 중에는 somatostatin의 감소 소견이 일관성 있게 보고되고 있다. 수용체에 대한 연구들은 아직 미미하다. 콜린계 수용체중 muscarinic receptor type 2(M2) 수용체의 저하가 선택적으로 일어나며, 전체적으로 nicotinic receptor의 수도 감소하는 것으로 보고된다. 기타 카테콜아민, 세로토닌, GABA 수용체 등은 큰 변화가 없다고 보고되고 있다. 향후 NMDA 수용체에 대한 연구가 주목된다. 알쯔하이머 질환에 있어서의 생물학적 지표로서 뇌척수액이나 말초혈액에서 보고되고 있는 것에는 특별한 게 없다. 단 뇌척수액내 somatostatin이 감소되어 있다는 것이 일관성 있게 보고되고 있고, 또한 혈소판 MAO 활성도가 증가된다. 하지만 MAO 활성도 증가는 정상 노화에서도 관찰되는 소견이다. 향후 뇌영상기법을 통한 연구들이 알쯔하이머 질환을 연구하는데 중요한 역할을 할 것이다. 현재 PET 검사로 발견되는 두정엽의 대사감소는 이 질환의 초기 생물학적 지표로 상정되고 있다. 이러한 연구들의 최종 목적은 환자들의 증상을 완화시키는데 있다. 현재로서는 콜린계 장애의 성상을 보다 정확히 규명하고 이에 대한 약물학적 접근을 해 나가는 것이 가장 이 목적에 접근해 있다고 생각된다.

자하거(紫河車) 약침(藥鍼)이 βA로 유도(誘導)된 Alzheimer`s Disease 병태(病態) 모델에 미치는 영향(影響)

이병훈 ( Byung Hun Lee ),박선영 ( Sun Young Park ),최철홍 ( Cheol Hong Choi ),이은경 ( Eun Kyung Lee ),정대규 ( Dae Kyoo Chung ) 대한한방신경정신과학회 2008 동의신경정신과학회지 Vol.19 No.2

Objective: Hominis Placenta is used in many cure, mainly treats a weak, chronic disease, especially senile. This research investigates the effect of the Hominis Placenta Herbal-Acupuncture Solution on Alzheimer`s disease. Method: The effects of the Hominis Placenta Herbal-Acupuncture Solution on (1) IL-1β protein, TNF-α protein, MDA, and CD68/CD11b (2) the behavior (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer`s diseased mice induced with βA were investigated. Results: 1. For the Hominis Placenta Herbal-Acupuncture Solution group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer`s disease induced by βA in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 2. The Hominis Placenta Herbal-Acupuncture Solution group suppressed the over-expression of IL-1β protein, TNF-α protein, MDA, and CD68/CD11b, in the mice with Alzheimer`s disease induced by βA. 3. The Hominis Placenta Herbal-Acupuncture Solution group reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer`s disease induced by βA. 4. The Hominis Placenta Herbal-Acupuncture Solution group reduced the Tau protein, GFAP protein, and presenilin1/2 protein, beta-secretase protein, (immunohistochemistry) of hippocampus in the mice with Alzheimer`s disease induced by βA. Conclusion: These results suggest that the Hominis Placenta Herbal-Acupuncture Solution group may be effective for the prevention and treatment of Alzheimer`s disease. Investigation into the clinical use of the Hominis Placenta Herbal-Acupuncture Solution for Alzheimer`s disease is suggested for future research. Objective: Hominis Placenta is used in many cure, mainly treats a weak, chronic disease, especially senile. This research investigates the effect of the Hominis Placenta Herbal-Acupuncture Solution on Alzheimer`s disease. Method: The effects of the Hominis Placenta Herbal-Acupuncture Solution on (1) IL-1β protein, TNF-α protein, MDA, and CD68/CD11b (2) the behavior (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer`s diseased mice induced with βA were investigated. Results: 1. For the Hominis Placenta Herbal-Acupuncture Solution group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer`s disease induced by βA in the Morris water maze experiment, which measured stop-through latency, and distance movement-through latency. 2. The Hominis Placenta Herbal-Acupuncture Solution group suppressed the over-expression of IL-1β protein, TNF-α protein, MDA, and CD68/CD11b, in the mice with Alzheimer`s disease induced by βA. 3. The Hominis Placenta Herbal-Acupuncture Solution group reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer`s disease induced by βA. 4. The Hominis Placenta Herbal-Acupuncture Solution group reduced the Tau protein, GFAP protein, and presenilin1/2 protein, beta-secretase protein, (immunohistochemistry) of hippocampus in the mice with Alzheimer`s disease induced by βA. Conclusion: These results suggest that the Hominis Placenta Herbal-Acupuncture Solution group may be effective for the prevention and treatment of Alzheimer`s disease. Investigation into the clinical use of the Hominis Placenta Herbal-Acupuncture Solution for Alzheimer`s disease is suggested for future research.

Platelets as a Source of Peripheral Aβ Production and Its Potential as a Blood-based Biomarker for Alzheimer’s Disease

Jae Seon Kang(강재선),Yun-Sik Choi(최윤식) 한국생명과학회 2020 생명과학회지 Vol.30 No.12

알츠하이머병은 점진적인 신경세포의 손상과 이로 인해 인지기능 장애를 유발하는 질병이다. 이 질환은 현재로서는 치료할 수 있는 질환이 아니고 진행을 멈추게 할 수 있는 방법이 없다. 그러나 초기에 알츠하이머병을 치료하는 것이 가장 효과적이므로 초기 진단은 증상을 관리할 수 있는 가장 좋은 기회를 제공할 수 있다. 알츠하이머병을 진단하기 위한 바이오마커로는 아밀로이드 베타(Aβ), 병적인 타우, 그리고 신경퇴화가 있고, Aβ의 축적, 인산화 타우는 뇌척수액이나 양전자 방출 단층촬영술을 통해 분석할 수 있다. 그러나 뇌척수액의 채취는 매우 침습적이고 양전자 방출 단층촬영술은 전문적인 고가의 장비가 필요하다. 지난 수십년 동안 빠르고 최소한의 침습성을 가진 바이오마커 분석법을 개발하기 위하여 혈액에 기반한 바이오마커 분석 기술이 연구되어 왔다. 그 중 주목할 만 한 발견이 혈장에서 Aβ의 주요 원천으로 혈소판과의 관련성이다. 아밀로이드 베타는 혈액-뇌 장벽을 통과할 수 있고 정상 상태에서는 뇌와 혈액 간 평형을 이루게 된다. 흥미롭게도, 여러 임상시험 결과 혈장에서 Aβ42/Aβ40 비율이 가벼운 인지장애 질환과 알츠하이머병에서 감소되어 있는 것을 증명하였다. 종합하면, 이러한 최근의 발견들은 침습성을 최소화한 알츠하이머병의 초기 진단 기술을 개발하는 데 이용될 수 있다. 본 총설에서, 저자들은 알츠하이머병의 바이오마커에 대한 최근 연구결과들, 특히 말초에서 Aβ를 생산하는 혈소판의 역할과 혈액 기반 바이오마커로서의 개발 가능성에 대해 고찰하였다. Alzheimer’s disease causes progressive neuronal loss that leads to cognitive disturbances. It is not currently curable, and there is no way to stop its progression. However, since medical treatment for Alzheimer’s disease is most effective in the early stages, early detection can provide the best chance for symptom management. Biomarkers for the diagnosis of Alzheimer’s disease include amyloid β (Aβ) deposition, pathologic tau, and neurodegeneration. Aβ deposition and phosphorylated tau can be detected by cerebrospinal fluid (CSF) analysis or positron emission tomography (PET). However, CSF sampling is quite invasive, and PET analysis needs specialized and expensive equipment. During the last decades, blood-based biomarker analysis has been studied to develop fast and minimally invasive biomarker analysis method. And one of the remarkable findings is the involvement of platelets as a primary source of Aβ in plasma. Aβ can be transported across the blood–brain barrier, creating an equilibrium of Aβ levels between the brain and blood under normal condition. Interestingly, a number of clinical studies have unequivocally demonstrated that plasma Aβ42/Aβ40 ratios are reduced in mild cognitive impairment and Alzheimer’s disease. Together, these recent findings may lead to the development of a fast and minimally invasive early diagnostic approach to Alzheimer’s disease. In this review, we summarize recent advances in the biomarkers of Alzheimer’s disease, especially the involvement of platelets as a source of peripheral Aβ production and its potential as a blood-based biomarker.

알쯔하이머병 환자에서 7분 선별검사를 이용한 인지장애의 평가

김인성(Inseong Kim),전진숙(Jin-Sook Cheon),오병훈(Byoung Hoon Oh) 대한임상노인의학회 2001 대한임상노인의학회지 Vol.2 No.4

연구목적 : 알쯔하이머 병은 인지기능이 점차로 저하되는 특징이 있다. 노화와 연관된 인지기능저하(age associated cognitive decline)와 경증 알쯔하이머 병은 구분이 어렵다. 경증 알쯔하이머 병을 선별하는 진단적 도구로서 한국인 알쯔하이머 환자들을 대상으로 7분 선별검사의 진단적 신뢰도와 영역별 특성을 살펴보았다. 방법 : DSM-IV에 의거하여 알쯔하이머 병으로 입원한 노인환자(N=28)에 대해서, 2주 이상의 병동적응 과정을 거친 후, MMSE-K 및 7분 선별검사(The 7 Minute Screen, 이하 7MS)로 인지기능을 평가하고 구조적 면담과 제반검사를 시행하였으며, 연령과 교육수준을 맞춘 건강한 대조군(N=30)에 대해서도 동일한 인지기능검사를 수행하여 그 결과를 비교 분석하였다. 7분 선별검사의 소검사는 Benton Temporal Orientation Test, Enhanced Cued Recall, Clock Drawing 및 Category Fluency 둥 네 가지로 구성되었다. 결과 : 1. 경증 알쯔하이머 병 환자군에서 7분 선별검사상 네 가지 소검사별 평균 점수는 지남력검사 62.07±40.28, 기억력 검사상 전체 8.43±3.04, Cued Recall 4.00±1.98, Uncued Recall 4.43±1.50, 시각ㆍ공간력검사 1.64±2.04, 언어유창성검사 8.79±2.36점이었으며, 네 가지 소검사에서 모두 대조군에 비해서 통계적으로 유의한 차이를 보였다(p<0.01). 2. 경증 알쯔하이머 병 환자군에서 7분 선별검사의 네 가지 소검사별 절취점의 결정은 지남력검사에서는 0, 기억력검사상 전체는 10개, 시각ㆍ공간력검사는 1점, 언어유창성검사 11개를 기준으로 그 이하에서 치매로 구분되었다. 3. 알쯔하이머 병 환자군에서 7분 선별검사의 네 가지 소검사 점수는 MMSE, 교육정도와 유의한 연관성이 있었다 결론 : 경증 알츠하이머 병 환자군에서 지남력, 기억력, 시각ㆍ공간력, 언어유창성 등의 인지영역에서 기능장애를 볼 수 있었다. Background : Alzheimer's disease is a typical neuropsychiatric disorder with declining of various cognitive function. It may be difficult to differentiated age-associated cognitive decline from mild Alzheimer's dementia. This study was done to identify cognitive disorders in Alzheimer's disease using the 7 Minute Screen. The '7 Minute Screen' test developed by Paul S. Soloman shows high sensitivity and specificity for screening of early Alzheimer' disease. Methods : The cognitive deficits were evaluated using the Mini Mental State Examination(MMSE) and the 7 Minute Screen(7 MS) in patients with Alzheimer's disease (N=28) as well as in age and education level matched healthy controls (N=30). Four individual tests of the 7 MS were consisted of the Benton Temporal Orientation Test, the Memory Test, the Clock Drawing and the Category Fluency. Results : 1. The average scores of four individual tests of the 7 MS for the Alzheimer's disease were 62.07±40.28 for the Benton Temporal Orientation Test, 8.43±3.04 for the Memory Test, 1.64±2.04 for the Clock Drawing and 8.79±2.36 for the Category Fluency. There were statistically significant differences between test scores of Alzheimer's disease and controls(p<0.01). 2. Cut-off poimts of individual test scores of the 7 Minute Screen in mild Alzheimer's disease were 0 for the Benton Temporal Orientation Test, 10 for the Memory Test, 1 for the Clock Drawing and 11 for the Category Fluency. Mild Alzheimer's disease obtained the scores below these levels. 3. Four individual test scores of the 7 MS seemed to have statistically significant association with MMSE and education level. Conclusion : Dysfuntion in cognitive areas such as orientation, memory, visuospatial abilities and verbal fluency could be found in mild Alzheimer's disease. 7 MS to be a valuable tool for the screening of Alzheimer's disease in the Korean elderly.

대조환(大造丸) 추출물이 ${\beta}$-amyloid로 유도된 Alzheimer's disease 병태(病態)모델에 미치는 영향

이지인,정대규,Lee, Ji-In,Chung, Dae-Kyoo 대한한방신경정신과학회 2007 동의신경정신과학회지 Vol.18 No.3

Ohjective: This research investigates the effect of the DJR on Alzheimer's disease. Method: 1.The effects of the DJR extract on IL.-$1{\beta}$, IL-6, TNF-${\alpha}$, cox-2, and NOS-II mRNA of BV2 microglia cell line treated with LPS; 2. the behavior: 3. the infarction area of the hippocampus, and brain tissue injury in Alzheimer's diseased mice induced with ${\beta}$A were investigated. Result: 1. The DJR extract suppressed the expression of IL-$1{\beta}$, IL-6 and TNF-${\alpha}$ mRNA in BV2 microglia cell line treated with LPS. 2. The DJR extract suppressed the expression of IL-$1{\beta}$, IL-6, and TNF-${\alpha}$ protein production in BV2 microglia cell line treated with LPS. 3. For the DJR extract group a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer's disease induced by .${\beta}$A in the Moms water maze experiment, which measured stop-through latency, and distance movement-through latency. 4. The DJR extract suppressed the over-expression of IL-$1{\beta}$ protein, TNF-${\alpha}$ protein and CD68/CD11b, in the mice with Alzheimer's disease induced by ${\beta}$A 5. The DJR extract reduced the infarction area of hippocampus, and controlled the injury of brain tissue in the mice with Alzheimer's disease induced by ${\beta}$A. 6. The DJR extract reduced the tau protein, GFAP protein, and presenilin1/2 protein (immunohistochemistry) of hippocampus in the mice with Alzheimer's disease induced by ${\beta}$A. Conclusion: These results suggest that the DJR extract may he effective for the prevention and treatment of Alzheimer's disease. Investigation into the clinical use of the DJR extract for Alzheimer's disease of suggested for future research.

Big Data Analysis of Genes Associated With Neuropsychiatric Disorders in an Alzheimer’s Disease Animal Model

Ham, Suji,Kim, Tae K.,Hong, Heeok,Kim, Yong S.,Tang, Ya-Ping,Im, Heh-In Frontiers Media S.A. 2018 Frontiers in neuroscience Vol.12 No.-

<P>Alzheimer’s disease is a neurodegenerative disease characterized by the impairment of cognitive function and loss of memory, affecting millions of individuals worldwide. With the dramatic increase in the prevalence of Alzheimer’s disease, it is expected to impose extensive public health and economic burden. However, this burden is particularly heavy on the caregivers of Alzheimer’s disease patients eliciting neuropsychiatric symptoms that include mood swings, hallucinations, and depression. Interestingly, these neuropsychiatric symptoms are shared across symptoms of bipolar disorder, schizophrenia, and major depression disorder. Despite the similarities in symptomatology, comorbidities of Alzheimer’s disease and these neuropsychiatric disorders have not been studied in the Alzheimer’s disease model. Here, we explore the comprehensive changes in gene expression of genes that are associated with bipolar disorder, schizophrenia, and major depression disorder through the microarray of an Alzheimer’s disease animal model, the forebrain specific PSEN double knockout mouse. To analyze the genes related with these three neuropsychiatric disorders within the scope of our microarray data, we used selected 1207 of a total of 45,037 genes that satisfied our selection criteria. These genes were selected on the basis of 14 Gene Ontology terms significantly relevant with the three disorders which were identified by previous research conducted by the Psychiatric Genomics Consortium. Our study revealed that the forebrain specific deletion of Alzheimer’s disease genes can significantly alter neuropsychiatric disorder associated genes. Most importantly, most of these significantly altered genes were found to be involved with schizophrenia. Taken together, we suggest that the synaptic dysfunction by mutation of Alzheimer’s disease genes can lead to the manifestation of not only memory loss and impairments in cognition, but also neuropsychiatric symptoms.</P>

가미보양환오탕(加味補陽還五湯) 열수추출물, 초미세분말제형이 Alzheimer`s Disease 병태 모델에 미치는 영향

서승호 ( Seung Ho Seo ),정인철 ( In Chul Jung ),이상룡 ( Sang Ryong Lee ) 대한한방신경정신과학회 2008 동의신경정신과학회지 Vol.19 No.3

Objective : This experiment was designed to investigate the effects of the KBHT hot water extract & ultra-fine powder on Alzheimer`s Disease Model Induced by βA. Method : The effects of the KBHT hot water extract on expression of proinflammatory cytokine mRNA in BV2 microglial celll cell line treated by lipopolysacchaide(LPS). The effects of the KBHT hot water extract & ultra-fine powder on (1) the behavior (2) AChE in serum (3) the infarction area of the hippocampus, and brain tissue injury in Alzheimer`s diseased mice induced with βA were investigated. Results : 1. The KBHT hot water extract suppressed the expression of proinflammatory cytokine mRNA in BV2 microglial cell line treated with LPS. 2. The KBHT hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer`s disease induced by βA in the Morris water maze experiment, which measured stop-through latency and distance movemet-through latency 3. The KBHT hot water extract & ultra-fine powder suppressed the over-expression of AChE activity in the serum of the mice with Alzheimer`s disease induced by βA. 4. The KBHT hot water extract & ultra-fine powder suppressed the expression of TNF-α, IL-1β protein significantly in the microglial cell of mice with Alzheimer`s disease induced by βA. 5. The KBHT ultra-fine powder reduced infarction area of hippocampus significantly in the mice with Alzheimer`s disease induced by βA. Conclusions : These results suggest that the KBHT hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer`s disease. Investigation into the clinical use of the PMCMT hot water extract & ultra-fine powder for Alzheimer`s disease is suggested for future research.

천왕보심단(天王補心丹) 열수추출물(熱水抽出物), 초미세분말제형(超微細粉末劑形)이 Alzheimer`s Disease 병태(病態) 모델에 미치는 영향(影響)

최강욱 ( Kang Wook Choi ),정인철 ( In Chul Jung ) 대한한방신경정신과학회 2008 동의신경정신과학회지 Vol.19 No.2

Objective : This experiment was designed to investigate the effect of the CBD hot water extract & ultra-fine Powder on Alzheimer`s Disease Model Induced by βA. Method : The effects of the CBD hot water extract on expression of interleukin-1 beta(IL-1β), TNF-α mRNA and production of IL-6, TNF-α in BV2 microglial cell line treated by lipopolysacchaide(LPS). The effects of the CBD hot water extract & ultra-fine powder on (1) the behavior (2) expression of IL-1β, tumor necrosis factor-alpha(TNF-α), (3) the infarction area of the hippocampus in Alzheimer`s diseased mice induced with βA were investigated. Result : The CBD hot water extract suppressed the expression of IL-1β, TNF-α mRNA in BV2 microglia cell line treated with LPS. The CBD hot water extract significantly suppressed the production of IL-1β, TNF-α in BV2 microglial cell line treated with LPS. The CBD hot water extract & ultra-fine powder a significant inhibitory effect on the memory deficit was shown for the mice with Alzheimer`s disease induced by βA in the Morris water maze experiment, which measured step-through latency and distance movement-through latency. The CBD hot water extract & ultra-fine powder significantly suppressed the expression of IL-1β and TNF-α protein in the microglial cell of mice with Alzheimer`s disease induced by βA. The CBD hot water extract & ultra-fine powder suppressed the over-expression of AChE activity in the serum of the mice with Alzheimer`s disease induced by βA. The CBD hot water extract & ultra-fine powder reduced infarction area of hippocampus, in the mice with Alzheimer`s disease induced by βA. Conclusions : These results suggest that the CBD hot water extract & ultra-fine powder may be effective for the prevention and treatment of Alzheimer`s disease. Investigation into the clinical use of the CBD hot water extract & ultra-fine powder for Alzheimer`s disease is suggested for future research.

알츠하이머성 치매와 그 예방식이에 대한 20대 성인 남녀의 인식도

임영빈(Young Been Yim),장영임(Young Im Jang),최아람(Ah Ram Choi),주지형(Jihyeung Ju) 충북대학교 생활과학연구소 2010 생활과학연구논총 Vol.14 No.1

The present study aimed to investigate recognition of adults in their 20's on Alzheimer's disease and its preventive diet. Subjects of this study were a total of 222 adults in their 20's (mean age: 24.4) in Korea. Major findings of this study were: 1) knowledge of the subjects on Alzheimer's disease and its preventive diets was scored as 17.4 (mean) out of 23 (75.6 out of 100); 2) 60.8% of the subjects answered the prevention of Alzheimer's disease should begin since they are in their 30's; 3) the subjects considered 'medical doctor' as the most appropriate educator for the preventive diets against Alzheimer's disease; 4) the higher interest of the subjects on Alzheimer's disease and its preventive diet. the higher recognition of the subjects on the need of knowledge and education. The present study suggest that adults in their 20's need to be better educated on the most right timing and appropriate educator for the prevention of Alzheimer's disease as well as fundamental knowledge for effectively making out their daily manu with the preventive diets.