Anti-amyloid-β disease-modifying therapies for Alzheimer′s disease: the dawn of a new era / 中华神经科杂志

Alzheimer′s disease (AD) is the most common neurodegenerative disease. Its etiology and pathogenesis remain unclear. Since its inception, the amyloid-β (Aβ) cascade hypothesis has dominated the field of AD research and has provided the intellectual framework for disease-modifying therapies. Nowadays, many Aβ-targeted therapies have been accelerated approval or received Food and Drug Administration′s breakthrough therapy designation which offers a new dawn for disease-modifying treating AD. This article reviews the research progress of clinical trials of Aβ-targeting modification therapies, and summarizes the lessons learned from the clinical failure with several classes of anti-Aβ drugs. Although many challenges remain, anti-Aβ therapies have become a promising treatment strategy for AD.

Elevated Levels of Naturally-Occurring Autoantibodies Against the Extracellular Domain of p75NTR Aggravate the Pathology of Alzheimer's Disease / 神经科学通报·英文版

The extracellular domain (p75ECD) of p75 neurotrophin receptor (p75NTR) antagonizes Aβ neurotoxicity and promotes Aβ clearance in Alzheimer's disease (AD). The impaired shedding of p75ECD is a key pathological process in AD, but its regulatory mechanism is largely unknown. This study was designed to investigate the presence and alterations of naturally-occurring autoantibodies against p75ECD (p75ECD-NAbs) in AD patients and their effects on AD pathology. We found that the cerebrospinal fluid (CSF) level of p75ECD-NAbs was increased in AD, and negatively associated with the CSF levels of p75ECD. Transgenic AD mice actively immunized with p75ECD showed a lower level of p75ECD and more severe AD pathology in the brain, as well as worse cognitive functions than the control groups, which were immunized with Re-p75ECD (the reverse sequence of p75ECD) and phosphate-buffered saline, respectively. These findings demonstrate the impact of p75ECD-NAbs on p75NTR/p75ECD imbalance, providing a novel insight into the role of autoimmunity and p75NTR in AD.

Systematic review on nine hallmarks of neurodegenerative disease

Alzheimer's disease (AD) and Parkinson's disease (PD) are the primary diseases in neurodegenerative diseases. Nowadays, AD is common in one of the ten individuals whose age is more than 65, and its prevalence is kept on increasing with aging. Very few treatments and no effective treatments are available for curing neurodegenerative diseases. Pathogenesis of neurodegenerative diseases, Alzheimer's disease, Parkinson's disease, and their association with the nine hallmarks of aging were clearly described in this review. Instability in genomic, attrition in telomere, alterations in epigenetics, proteostasis loss, dysfunction in mitochondria, senescence in cells, sensing of deregulated nutrition, exhaustion of stem cells, and alterations in intercellular communication are the nine biological hallmarks of Aging. Improving the medical facilities for neurodegenerative diseases is very much essential. Doctors and researchers are doing surplus research to overcome the unavailability of proper treatments for such neurodegenerative diseases. Reason and the causes behind the diseases and their effects are explained in this review to enhance the further research to help the society.

Biofluid Biomarkers of Alzheimer's Disease: Progress, Problems, and Perspectives / 神经科学通报·英文版

Since the establishment of the biomarker-based A-T-N (Amyloid/Tau/Neurodegeneration) framework in Alzheimer's disease (AD), the diagnosis of AD has become more precise, and cerebrospinal fluid tests and positron emission tomography examinations based on this framework have become widely accepted. However, the A-T-N framework does not encompass the whole spectrum of AD pathologies, and problems with invasiveness and high cost limit the application of the above diagnostic methods aimed at the central nervous system. Therefore, we suggest the addition of an "X" to the A-T-N framework and a focus on peripheral biomarkers in the diagnosis of AD. In this review, we retrospectively describe the recent progress in biomarkers based on the A-T-N-X framework, analyze the problems, and present our perspectives on the diagnosis of AD.

Prevention and treatment of Alzheimer′s disease: challenges and perspectives / 中华神经科杂志

Alzheimer′s disease (AD), the most common neurodegenerative disease, is a major challenge in China and all the world. However, the pathogenesis of AD remains unclear, and no disease-modifying therapies are available to prevent or treat the disease. Amyloid-beta (Aβ) and hyperphosphorylated tau protein are key pathological molecules of AD. A series of clinical trials targeting Aβ, tau protein and neuroinflammation have been carried out in the past 20 years, but none of them have been successful in attenuating the cognitive decline so far. This paper discusses the challenges of the current clinical trials of AD and proposes future directions for the research of AD prevention and treatment.

The Essentials of Biochemistry of the Proteins as Related to Alzheimer’s Disease: A Review

Amyloid plaques and Tau tangles, constitute the pathological hallmarks of the brains of the patients suffering from Alzheimer’s disease. They are identified as far back as 1996 by Alois Alzheimer, a German psychiatrist and neuropathologist, but till this date, how they produce neuronal death remained an enigma. The amyloid cascade theory held its sway until recent times until the emphasis is shifted to the metabolites of amyloid Beta precursor protein (APP). Several metabolites of APP are formed depending on by which pathway, the APP is metabolized, either by the non - amyloidogenic pathway (forming ? - C terminal fragment - CTF? / C83 and the N - terminal fragment sAPP? / P3 and the APP intracellular domain AICD). Or amyloidogenic pathways. ( Forming extracellular A? and APP intracellular domain - AICD). The hyperphosphorylation is held responsible for the tau protein tangles. The over activity of the tau kinases or the failure of inhibition by the tau phosphatases i s implicated, in tau tangle deposits. These biochemical aspects of AD assumed importance in connection with the interventional therapeutic strategies that are developed in the years bygone, as well as those still are in the developing stage. In keeping with this fact, it is attempted to review the essentials of the biochemical aspects of the involved proteins, as related to AD, in this article

β-Sitosterol treatment attenuates cognitive deficits and prevents amyloid plaque deposition in amyloid protein precursor/presenilin 1 mice

Alzheimer's disease (AD) is the most common neurodegenerative disorder causing dementia worldwide, and is mainly characterized by aggregated β-amyloid (Aβ). Increasing evidence has shown that plant extracts have the potential to delay AD development. The plant sterol β-Sitosterol has a potential role in inhibiting the production of platelet Aβ, suggesting that it may be useful for AD prevention. In the present study, we aimed to investigate the effect and mechanism of β-Sitosterol on deficits in learning and memory in amyloid protein precursor/presenilin 1 (APP/PS1) double transgenic mice. APP/PS1 mice were treated with β-Sitosterol for four weeks, from the age of seven months. Brain Aβ metabolism was evaluated using ELISA and Western blotting. We found that β-Sitosterol treatment can improve spatial learning and recognition memory ability, and reduce plaque load in APP/PS1 mice. β-Sitosterol treatment helped reverse dendritic spine loss in APP/PS1 mice and reversed the decreased hippocampal neuron miniature excitatory postsynaptic current frequency. Our research helps to explain and support the neuroprotective effect of β-Sitosterol, which may offer a novel pharmaceutical agent for the treatment of AD. Taken together, these findings suggest that β-Sitosterol ameliorates memory and learning impairment in APP/PS1 mice and possibly decreases Aβ deposition.

Association of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease in a Chinese Cohort / 神经科学通报·英文版

To evaluate whether the polygenic profile modifies the development of sporadic Alzheimer's disease (sAD) and pathological biomarkers in cerebrospinal fluid (CSF), 462 sAD patients and 463 age-matched cognitively normal (CN) controls were genotyped for 35 single-nucleotide polymorphisms (SNPs) that are significantly associated with sAD. Then, the alleles found to be associated with sAD were used to build polygenic risk score (PRS) models to represent the genetic risk. Receiver operating characteristic (ROC) analyses and the Cox proportional hazards model were used to evaluate the predictive value of PRS for the sAD risk and age at onset. We measured the CSF levels of Aβ42, Aβ42/Aβ40, total tau (T-tau), and phosphorylated tau (P-tau) in a subgroup (60 sAD and 200 CN participants), and analyzed their relationships with the PRSs. We found that 14 SNPs, including SNPs in the APOE, BIN1, CD33, EPHA1, SORL1, and TOMM40 genes, were associated with sAD risk in our cohort. The PRS models built with these SNPs showed potential for discriminating sAD patients from CN controls, and were able to predict the incidence rate of sAD and age at onset. Furthermore, the PRSs were correlated with the CSF levels of Aβ42, Aβ42/Aβ40, T-tau, and P-tau. Our study suggests that PRS models hold promise for assessing the genetic risk and development of AD. As genetic risk profiles vary among populations, large-scale genome-wide sequencing studies are urgently needed to identify the genetic risk loci of sAD in Chinese populations to build accurate PRS models for clinical practice.

Alzheimer's Disease Diagnosis Using Misfolding Proteins in Blood

Alzheimer's disease (AD) is pathologically characterized by a long progressive phase of neuronal changes, including accumulation of extracellular amyloid-β (Aβ) and intracellular neurofibrillary tangles, before the onset of observable symptoms. Many efforts have been made to develop a blood-based diagnostic method for AD by incorporating Aβ and tau as plasma biomarkers. As blood tests have the advantages of being highly accessible and low cost, clinical implementation of AD blood tests would provide preventative screening to presymptomatic individuals, facilitating early identification of AD patients and, thus, treatment development in clinical research. However, the low concentration of AD biomarkers in the plasma has posed difficulties for accurate detection, hindering the development of a reliable blood test. In this review, we introduce three AD blood test technologies emerging in South Korea, which have distinctive methods of heightening detection sensitivity of specific plasma biomarkers. We discuss in detail the multimer detection system, the self-standard analysis of Aβ biomarkers quantified by interdigitated microelectrodes, and a biomarker ratio analysis comprising Aβ and tau.

Effect of Danggui Shaoyaosan on Copper Ion-mediated Aβ Aggregation in AD Cell Model / 中国实验方剂学杂志

Objective:To investigate the effect of copper ion(Cu2+) on the aggregation and neurotoxicity of Aβ, and affirm the role of Danggui Shaoyaosan in vitro,the Neuroblastoma (SH-SY5Y) cells treated with β-amyloid 1-42 (Aβ1-42) and Cu2+ were used as a vitro models of Alzheimer's disease(AD). Method:Aβ 1-42 (20 μmol·L-1) was reacted with different concentrations of copper sulfate (CuSO4,20,40 μmol·L-1), and then the thioflavine T (ThT) staining method was used to detect the Aβ aggregation state. The Aβ aggregation status was also detected by ThT staining in the Aβ1-42-Cu2+ group(20+20 μmol·L-1), and Danggui Shaoyaosan groups(1.6,3.2,6.4 mg·L-1).The SH-SY5Y cells were cultured and incubated with different concentrations of Aβ1-42(1.25,2.5,5,10,20,40 μmol·L-1) and Danggui Shaoyaosan(1.6, 3.2, 6.4,12.8 mg·L-1) for 24 h. Subsequently, SH-SY5Y cells were incubated with Aβ1-42 (20 μmol·L-1) and CuSO4(20 μmol·L-1) in the Aβ1-42-Cu2+ group, and incubated with Aβ1-42 (20 μmol·L-1), Danggui Shaoyaosan (1.6 mg·L-1) and CuSO4 (20 μmol·L-1) in Danggui Shaoyaosan group. Control group was added with the medium. After 24 h of co-action, the cell viability was detected by the methylthiazolyl tetrazolium (MTT) assay. The morphology of the cells was photographed by microscopy. The intracellular extracellular Aβ1-42 aggregation was detected by Western blot. Result:Cu2+ and Aβ1-42 bound to more and larger Aβ aggregates compared with the Aβ1-42 group. Compared with the normal group, cell viability was significantly reduced (PPβ1-42 aggregation was increased(PPβ-Cu2+ (PPβ1-42 protein (PPConclusion:Cu2+ can increase the aggregation and toxicity of Aβ; Danggui Shaoyaosan can significantly reduce the damage of SH-SY5Y cells induced by Cu2+-mediated Aβ aggregation, promote Aβ endocytosis, reduce extracellular Aβ aggregation and increase cell viability.

Focused ultrasound and Alzheimer's disease: a systematic review / Ultrassonografia focalizada e doença de Alzheimer: uma revisão sistemática

ABSTRACT Alzheimer's disease (AD) affects millions of people, however, there is still no effective treatment. The use of focused ultrasound with microbubbles (FUS-MB) for the opening of the blood-brain barrier has been recently studied and may become a promising therapeutic target. Objective: To discuss the use of FUS-MB for the treatment of AD and to present some of the techniques used. Methods: A systematic review was performed of MEDLINE/PubMed and Biblioteca Virtual em Saúde (BVS) services, using the keywords: focused ultrasound, Alzheimer, amyloid-b. Original articles were included in the study; studies that did not focus on Alzheimer's treatment were excluded. Results: Fifteen original studies were selected. Preclinical trials were able to reduce amyloid-b plaques and tau phosphorylation, improving cognitive performance in AD animals. Conclusion: The results are very promising, but the therapy still requires maturation. Further studies are needed to systematize all the techniques used and their effects in order to enable use in humans.

RESUMO A doença de Alzheimer (DA) afeta milhões de pessoas, porém, ainda não há um tratamento efetivo. O uso de ultrassonografia focalizada com microbolhas (FUS-MB) para a abertura da barreira hematoencefálica (BHE) tem sido objeto de estudos recentes, podendo tornar-se um alvo terapêutico bastante promissor. Objetivo: Discutir o uso da FUS-MB para o tratamento da DA e apresentar algumas das técnicas utilizadas. Métodos: Revisão sistemática através dos serviços MEDLINE/PubMed e Biblioteca Virtual em Saúde (BVS), através das seguintes palavras-chaves: focused ultrasound, Alzheimer, amyloid-b. Foram incluídos no estudo artigos originais. Foram excluídos estudos que não tinham o tratamento do Alzheimer como foco. Resultados: Foram selecionados 15 estudos originais. Os resultados pré-clínicos são positivos para redução de placas amiloides, fosforilação da proteína tau e sobre desempenho cognitivo de animais com DA. Conclusão: Os resultados são promissores, mas terapia ainda necessita de aperfeiçoamento, necessitando de mais estudos que sistematize todas as técnicas e seus efeitos, para ser possível o seu uso em humanos.

Clinical Research on Alzheimer's Disease: Progress and Perspectives / 神经科学通报·英文版

Alzheimer's disease (AD), the most common type of dementia, is becoming a major challenge for global health and social care. However, the current understanding of AD pathogenesis is limited, and no early diagnosis and disease-modifying therapy are currently available. During the past year, significant progress has been made in clinical research on the diagnosis, prevention, and treatment of AD. In this review, we summarize the latest achievements, including diagnostic biomarkers, polygenic hazard score, amyloid and tau PET imaging, clinical trials targeting amyloid-beta (Aβ), tau, and neurotransmitters, early intervention, and primary prevention and systemic intervention approaches, and provide novel perspectives for further efforts to understand and cure the disease.

Beta-amyloid imaging in dementia / 영남의대학술지

Alzheimer's disease (AD) is a neurodegenerative disorder associated with extracellular plaques, composed of amyloid-beta (Aβ), in the brain. Although the precise mechanism underlying the neurotoxicity of Aβ has not been established, Aβ accumulation is the primary event in a cascade of events that lead to neurofibrillary degeneration and dementia. In particular, the Aβ burden, as assessed by neuroimaging, has proved to be an excellent predictive biomarker. Positron emission tomography, using ligands such as ¹¹C-labeled Pittsburgh Compound B or ¹⁸F-labeled tracers, such as ¹⁸F-florbetaben, ¹⁸F-florbetapir, and ¹⁸F-flutemetamol, which bind to Aβ deposits in the brain, has been a valuable technique for visualizing and quantifying the deposition of Aβ throughout the brain in living subjects. Aβ 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.

Effect of α7nAchR gene 713T>C mutation on cognitive function and Aβ expression in AD mice / 重庆医学

Objective To investigate the effect of α7nAchR gene 713T>C mutation on the cognitive function and Aβ expression in Alzheimer′s disease(AD)mice.Methods Twenty APPSwe transgenic APPa7KO mice(6 months old,α7nAchR gene knockout)were divided into the mutation type group and wild type group according to the random number table method,10 cases in each group.The mutation type and wild type of AVV-α7nAchR cDNA were respectively injected by lateral ventricle,once per month,for 6 times.The change of cognitive function in mice was examined by Morris water maze.The ELISA method was used to detect Aβ 40 and Aβ 42 expression levels.The Aβ plaque deposit situation was detected by the immunochemical method.Results Compared with the mice in the wild type group,the escape latency and the time of first time to find the platform of the mice in the mutation type group were significantly extended,while Hippocampal Aβ40 and Aβ42 expression levels were significantly increased,the difference was statistically significant(P＜0.05).Conclusion α7nAchR gene 713T>C mutation aggravates the cognitive function impairments in AD mice and hippocampal neuron Aβ expression level.

Effects of Dihuang Yinzi on RAGE/ROS/Apoptosis Pathway in SH-SY5Y Cells Induced by Aβ1-42 / 广州中医药大学学报

Objective To investigate the effects of Dihuang Yinzi (DY) on the receptor for advanced glycation end-products(RAGE)/reactive oxygen species(ROS)/apoptosis pathway in SH-SY5Y cells induced by amyloid-beta1-42 (Aβ1-42) oligomer. Methods Firstly, we adopted methyl thiazolyl tetrazolium(MTT) method to detect the cell vitality in fetal bovine serum (FBS) group, blank serum group, and low-, middle- and high- dose DY-containing serum groups, so as to confirm the optimal concentration and treatment time of DY-containing serum. Secondly, we applied MTT method to detect cell vitality and applied Annexin V/propidium iodide (PI) staining method to observe the apoptosis of SH-SY5Y cells treated with 0~20 μmol/L Aβ1-42 for 24 and 48 h, so as toconfirm the optimal concentration and treatment time of Aβ1-42 for establishing Alzheimer's disease (AD) model in vitro. Thirdly, MTT method was used for the detection of cell vitality, and Annexin V/PI staining method was used for detection of the apoptosis of SH-SY5Y cells in blank serum group, model group, western medicine control group and low-, middle-and high-dose DY-containing serum groups, and Dihydroethidium (DHE) method was used for the assay of ROS contents, so as to observe the effect of DY on the recovery of injured SH-SY5Y cells induced by Aβ1-42. Finally, we applied Western blot method to detect the expression level of RAGE in SH-SY5Y cells of blank group, model group and DY-containing serum group; after Aβ1-42-induced SH-SY5Y cells were transfected with RAGE gene, we adopted DHE staining method and Annexin V/PI staining method to detect ROS content and cell apoptotic rate in all of the above groups, so as to observe the effect of DY on SH-SY5Y cell apoptosis and RAGE expression. Results The cell vitalities were increased in low- and middle-dose DY-containing serum groups at 24 h (P < 0.05 or P < 0.01 compared with that in the blank serum group). The conditions for the establishment of AD model in vitro were as follows: the optimal concentration of Aβ1-42 was 5μmol/L, and the treatment time was 24 h. The cell vitalities were significantly enhanced, the cell apoptotic rate and ROS content were significantly lowered in Aβ1-42-induced SH-SY5Y cells of the medication groups(P <0.05 or P < 0.01 compared with those in the model group) , and the cell vitality was the highest and the cell apoptotic rate was the lowest in the middle-dose DY-containing serum group. The RAGE expression level was decreased in Aβ1-42-induced SH-SY5Y cells of the middle-dose DY-containing serum group(P < 0.05 compared with that in the model group) . ROS content and cell apoptotic rate were decreased in Aβ1-42-induced SH-SY5Y cells transfected with RAGE gene in the middle-dose DY-containing serum group (P<0.01). Conclusion DY may play an anti-oxidative role through inhibiting the production of ROS and cell apoptosis, thus to suppress RAGE protein and to achieve the preventive and therapeutic effect for AD.

Whole Brain Voxel-Wise Analysis of Cerebral Retention of Beta-Amyloid in Cognitively Normal Older Adults Using ¹⁸F-Florbetaben

OBJECTIVE: Recently developed 18F-labelled amyloid beta (Aβ) positron emission tomography (PET) tracers have demonstrated potentials to enable more prevalent application of amyloid imaging in the clinical setting. The aim of this study is to demonstrate cerebral retention of Aβ in cognitively normal older adults, by implementing voxel-based analysis on images acquired from 18F-Florbetaben amyloid PET. METHODS: Fifty cognitive normal elderly subjects were recruited and included in the study. Demographic data and cognitive measurements were collected. Magnetic resonance imaging (MRI) and ¹⁸F-Florbetaben PET data were obtained followed by whole brain voxel-based analysis. RESULTS: Compared to the florbetaben (FBB) (−) counterpart, FBB (+) showed significantly higher Aβ deposition in the brain regions comprising anterior cingulate, middle cingulate, posterior cingulate and precuneus (family wise error corrected p < 0.05). There was no significant correlation between amyloid retention and cognitive functions. CONCLUSION: Our results confirms previous results regarding Aβ deposition by using ¹⁸F-Florbetaben, demonstrating potentials in application of 18F-Florbetaben PET imaging in clinical settings.

Puerarin alleviates cognitive impairment and tau hyperphosphorylation in APP/PS1 transgenic mice / 中国中药杂志

To observe the effect of puerarin on learning and memory function and tau phosphorylation in APP/PS1 transgenic mice, drugs were administered to 3-month old APP/PS1 transgenic mice. Learning and memory function of mice were assessed by Morris water maze test 3 months after treatment. Animals were decapitated after behavioral test. The levels of Aβ were detected by ELISA, the expression of protein [tau, phosphorylated tau, GSK3β and p-GSK3β(Ser9)] were assessed by Western blot. Morris water maze test showed that the escape latency of APP/PS1 double transgenic mice was significantly longer than that of the normal control group, and the residence time of the original quadrant was significantly shorter. The escape latency of puerarin group was significantly shorter and the residence time of the original quadrant was prolonged compared with the model group. Compared with the normal control group, the levels of Aβ in the cortex of APP/PS1 transgenic mice were increased, the expression of phosphorylated tau was significantly increased, and the expression of phosphorylated GSK3β(Ser9) protein was decreased. Treatment with puerarin, the latency of APP/PS1 transgenic mice was significantly reduced, the level of Aβ was decreased, the expression of phosphorylated tau was significantly decreased, and the expression of phosphorylated GSK3β(Ser9) protein was increased. Puerarin improves the learning and memory impairment by reducing the formation of Aβ, activating the GSK3β signaling pathway, inhibiting the phosphorylation of tau in APP/PS1 double transgenic mice.

Research progress in pharmacological effects of Uncaria Hook on Alzheimer disease models / 药学学报

The most common neurodegenerative disease, Alzheimer disease (AD) constitutes the majority of all senile dementia cases. Extending life expectancy contributes to the increased incidence of AD, which is a serious threat to the quality of life of the elderly. The etiology and pathogenesis of AD are not absolutely clear. There are various kinds of hypotheses, such as abnormal phosphorylation of tau proteins, amyloid-beta protein toxicity, gene mutation, degeneration of cholinergic system, neuroinflammation, oxidative stress. Based on the above-mentioned theories, lots of studies of Uncaria Hook have been conducted in Alzheimer disease models. In this paper, we reviewed the latest research of Uncaria Hook on Alzheimer disease models to provide reference for further development of Uncaria Hook's medicinal potential.

Spinosin, a C-Glucosylflavone, from Zizyphus jujuba var. spinosa Ameliorates Abeta1-42 Oligomer-Induced Memory Impairment in Mice

Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive memory loss and neuronal cell death. Although numerous previous studies have been focused on disease progression or reverse pathological symptoms, therapeutic strategies for AD are limited. Alternatively, the identification of traditional herbal medicines or their active compounds has received much attention. The aims of the present study were to characterize the ameliorating effects of spinosin, a C-glucosylflavone isolated from Zizyphus jujuba var. spinosa, on memory impairment or the pathological changes induced through amyloid-beta1-42 oligomer (AbetaO) in mice. Memory impairment was induced by intracerebroventricular injection of AbetaO (50 muM) and spinosin (5, 10, and 20 mg/kg) was administered for 7 days. In the behavioral tasks, the subchronic administration of spinosin (20 mg/kg, p.o.) significantly ameliorated AbetaO-induced cognitive impairment in the passive avoidance task or the Y-maze task. To identify the effects of spinosin on the pathological changes induced through AbetaO, immunohistochemistry and Western blot analyses were performed. Spinosin treatment also reduced the number of activated microglia and astrocytes observed after AbetaO injection. In addition, spinosin rescued the AbetaO-induced decrease in choline acetyltransferase expression levels. These results suggest that spinosin ameliorated memory impairment induced through AbetaO, and these effects were regulated, in part, through neuroprotective activity via the anti-inflammatory effects of spinosin. Therefore, spinosin might be a useful agent against the amyloid b protein-induced cognitive dysfunction observed in AD patients.

Prolonged oral administration of Gastrodia elata extract improves spatial learning and memory of scopolamine-treated rats / 한국실험동물학회지

Gastrodia elata (GE) is traditionally used for treatment of various disorders including neurodegenerative diseases such as Alzheimer's disease. To investigate the neuroprotective effect of GE, amyloid-beta peptide (Abeta)-treated PC12 cells were cultured with GE aqueous extract. In vitro assay demonstrated that 50 microM of pre-aggregated Abeta was lethal to about a half portion of PC12 cells and that Abeta aggregate-induced cell death was significantly decreased with GE treatment at < or =10 mg/mL in a dose-dependent manner. To further examine in vivo cognitive-improving effects, an artificial amnesic animal model, scopolamine-injected Sprague-Dawley rats, were orally administered the extract for 6 weeks followed by behavioral tests (the passive avoidance test and Morris water maze test). The results showed that an acute treatment with scopolamine (1 mg/kg of body weight) effectively induced memory impairment in normal rats and that the learning and memory capability of scopolamine-treated rats improved after prolonged administration of GE extract (50, 250 and 500 mg/kg of body weight for 6 weeks). These findings suggest that a GE regimen may potentially ameliorate learning and memory deficits and/or cognitive impairments caused by neuronal cell death.