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Panax ginseng, a venerable herb in traditional Chinese medicine, boasts a rich history of usage in the treatment of dementia, particularly in its various manifestations. However, despite its long-standing popularity and empirical evidence of effectiveness, the precise mechanisms underlying its therapeutic actions have remained elusive. Currently, research on pharmacodynamic components and mechanisms predominantly utilizes serum pharmacology and metabolomics research methods that are based on liquid chromatography-mass spectrometry technology. However, these methods are unable to capture the spatial distribution information of relevant substances, leading to a lack of comprehensive understanding of the pharmacodynamic components and their underlying mechanisms. To bridge this gap in knowledge, a method of spatial metabolomics and air flow assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), was used to delve into the molecular mechanisms of Panax ginseng in treating Alzheimer’s disease (AD). The pharmacodynamic results demonstrated that Panax ginseng extract can significantly improve the state of brain pathological damage and spatial learning memory ability in AD model rats. This finding highlights the potential of ginseng as a therapeutic agent in AD management. Furthermore, the metabolomics analysis revealed that Panax ginseng modulates the levels of 19 biomarkers that are intricately linked to AD. These biomarkers span across 8 key metabolic pathways, including arginine and proline metabolism, purine metabolism, the tricarboxylic acid (TCA) cycle, and fatty acid metabolism. These pathways are essential for maintaining neuronal health and function, and their dysregulation is often associated with the pathogenesis of AD. Importantly, the study identified 7 active ginseng constituents that accumulate in brain tissue. These compounds work in a holistic manner to treat AD by modulating metabolites related to neuroinflammation, neuronal damage, energy deficits, and abnormal fatty acid metabolism. The comprehensive approach suggests that Panax ginseng may offer a multifaceted therapeutic strategy for AD. The unique capabilities of mass spectrometry imaging allow to analyze the spatial distribution of both endogenous and exogenous substances in parallel. This correspondence not only provides a deeper understanding of the specific effects of drug components, but also sheds light on how these components interact with the body’s endogenous metabolic networks to exert their therapeutic effects. In conclusion, the study provides new light on the mechanisms of action of Panax ginseng in treating AD and paves the way for future research and clinical applications of the ancient herb.

Alzheimer's disease (AD) is a neurodegenerative disease with age-related cognitive decline. Sphingosine-1-phosphate receptor 2 (S1PR2) is involved in a variety of cellular processes and has been shown to play an important role in nervous system development. This study aimed to investigate the effects and possible mechanism of S1PR2 on Aβ25-35 induced cell model damage of AD. In this study, SH-SY5Y cells were induced by Aβ25-35 to construct a cell damage model, and the expression of S1PR2 in cells was interfered by targeting sequence. The protein and gene expression levels of S1PR2 were detected by Western blot and RT-PCR. It was found that the expression of S1PR2 was significantly increased at mRNA and protein levels in Aβ25-35 -induced SH-SY5Y cell model (P<0.01), and its expression was significantly decreased after S1PR2 intervention (P<0.001). The cell proliferation activity was detected by CCK8, and apoptosis was detected by flow cytometry. The results showed that the proliferation activity of Aβ25-35 induced SH-SY5Y cells was significantly increased, and apoptosis was decreased after S1PR2 intervention (P<0.01). The protein levels of APP, Tau, p-Tau, and PSD95 in cells were detected by Western blot to analyze the effect of S1PR2 on the pathology of AD. It was found that after S1PR2 intervention, the expressions of APP, Tau, and p-Tau in the AD cell model were significantly decreased (P<0.001), and the expression of synaptic protein PSD95 was increased (P<0.001), which could significantly improve the pathological damage in Aβ25-35 -induced SH-SY5Y cell model. In addition, ATP production was detected by the kit, and ROS content and mitochondrial membrane potential were detected by flow cytometry to analyze the mitochondrial function. Results found that ATP production and mitochondrial membrane potential was significantly decreased, whereas the ROS content was increased in Aβ25-35 induced SH-SY5Y cells (P<0.001). Intervention with S1PR2 significantly increased ATP production and mitochondrial membrane potential, but decreased ROS content(P<0.001). Finally, the protein levels of the AKT/mTOR pathway were detected by Western blot. The results showed that S1PR2 significantly inhibited the activation of the AKT/mTOR pathway induced by Aβ25-35 in SH-SY5Y cells. In conclusion, S1PR2 may be involved in the pathogenesis of Aβ25-35 -induced SH-SY5Y cells by promoting mitochondrial function through the AKT/mTOR pathway. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Hebei University of Science & Technology is the property of Hebei University of Science & Technology, Journal of Hebei University of Science & Technology and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Computer Engineering & Applications is the property of Beijing Journal of Computer Engineering & Applications Journal Co Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Intelligence diagnosis has been widely studied in the diagnosis of Alzheimer's disease (AD), but existing intelligent modeling methods cannot make full use of the multi-modal data feature information. As a result, the recognition accuracy is not high in the diagnosis of disease in the early stage. In order to improve the diagnosis effect of AD and its early stage, a classification method of Alzheimer's disease integrating individual feature and fusion feature is proposed. Firstly, the hypergraph convolutional network (HGCN) is used to extract features from the data of three modalities of MRI (magnetic resonance imaging), PET (positron emission computed tomography), and CSF (cerebro-spinal fluid) to obtain the high-order deep feature. At the same time, the data of these three modalities are fused through low-rank multimodal fusion to obtain hidden correlation features among multiple modalities. Finally, a multi-view classifier is used to comprehensively classify the above-obtained features. The ADNI dataset is used to classify AD in multiple groups of tasks to verify the proposed method. Compared with other state-of-the-art methods, the proposed method effectively improves the classification accuracy in the early stage of the disease while ensuring the classification effect of the AD stage.

As global aging worsens and deep learning advances, the imaging classification of Alzheimer’s disease (AD) based on deep learning has become a hot topic of research. This paper reviewed the common deep learning models, evaluation criteria and public datasets in AD imaging classification tasks, discussed the application of different image modalities in AD imaging classification. The content was focused on the improvement of deep learning models applied to AD imaging classification. The studies of model interpretability were also introduced. Finally, the paper summarized and compared the classification models mentioned, identified the brain regions related to AD image classification, and outlined the future research directions in this field.

Alzheimer's disease (AD) is an age-related neurodegenerative disease with insidious onset and slow progression. The progression of AD from only brain pathological changes to clinically identifiable cognitive changes is affected by a variety of environmental factors inside and outside the organism and can last for decades. Cognitive impairment is an important clinical feature of AD that impairs the quality of life of the elderly in their later years, and the available drugs for the treatment of AD have failed to cure the disease, indicating the importance of early prevention of AD-related cognitive impairment. Most current research on the relationship between nutrition and AD takes nutritional intervention as a preventive method for AD-related cognitive impairment. The role of dietary supplement or restriction on AD-related cognitive impairment is related to multiple pathways. It is worth noting that the gut microbiome, as an important medium in the effect of dietary on the host, can influence cognitive function through the "microbial-gut-brain axis". The antioxidant and anti-inflammatory properties of some foods are beneficial for improving cognitive function. In this paper, relevant studies in recent years were analyzed to discuss the effects of certain single nutrients (vitamins, polyphenols, and long chain polyunsaturated fatty acids) and overall nutritional patterns (Mediterranean diet, dietary approaches to stop hypertension diet, Mediterranean-DASH intervention for neurodegenerative delay, and ketogenic diet) on cognitive function, so as to provide ideas and reference for the prevention and treatment of AD-related cognitive impairment.

Objective To explore the risk of Alzheimer′s disease (AD) transmitted by blood transfusion. Methods There were 10 APP/PS1 mice of 3, 6 and 9 months old, half female and half male, and the cognitive and behavioral abilities of C57 mice of the same age were measured, and the blood of the oldest APP/PS1 mice with no behavioral changes were collected to detect the contents of Aβ40 and Aβ42. The polymers Aβ40 and Aβ42 were prepared and Western blotting analysis was conducted. Kunming mice aged from 6 to 7 months were randomly divided into 6 groups (10 mice/ group, half male and half female). The blood of APP/PS1 mice was injected intravenously in experimental group 1-2(100 μL/mouse) with high frequency injection (3 times/week) and low frequency injection (1 time/week), respectively. In experimental group 3-4, Aβ40 and Aβ42 polymerized mixture (100 μL/mouse) were injected in high frequency and low frequency, respectively. The control group 1-2 was injected with the same amount of normal saline, with high frequency and low frequency, respectively. The above groups were injected for 4 weeks, and the cognitive and behavioral abilities were tested and analyzed one week after injection. Finally, the contents of Aβ40 and Aβ42 in blood of Kunming mice were detected. Results Change in cognitive and behavioral ability showed in 9 months old APP/PS1 mice, but not in 3 and 6 months old APP/PS1 mice. The contents of Aβ40 and Aβ42 (pg/mL) in blood of 6-7 months old APP/PS1 mice were 418.40±2.18 and 15.68±0.20, respectively. Except for monomers, most of the polymerized mixtures of Aβ40 and Aβ42 were dimers and trimers. In both high frequency and low frequency, Kunming mice transfused with blood of APP/PS1 mice (experimental group 1-2) showed a certain degree of anxiety-like behavior and short-term memory shortening in open-field test and conditioned fear test, but without significant difference. There was no significant difference in open field test, new object recognition, Barnes maze and cognitive behavior analysis of conditioned fear between experimental group 3-4 and the control group. The levels of blood Aβ40 and Aβ42(pg/mL) of Kunming mice detected by ELISA were 10.30±0.08 and 3.360±0.005, respectively, and there was no significant difference between the two groups. Conclusion Blood transfusion of APP/PS1 mice and the mixture of Aβ40 and Aβ42 have no significant effect on the cognitive function of healthy Kunming mice in a short time, and the risk of AD transmission is relatively low.

Objective·To propose a theoretical method based on geosciences for the expression and quantitative description of the surface morphology of the cerebral cortex.Methods·Eighty-five samples of normal cognition (NC) and 84 samples of Alzheimer′s disease (AD) were downloaded from the Alzheimer′s Disease Neuroimaging Initiative (ADNI) database, and the cerebral cortex data of magnetic resonance imaging (MRI) images of the human brain were extracted by using SPM 12 software package. The undulating cerebral cortex image was mapped into the point cloud data after three-dimensional reconstruction, and the digital elevation model (DEM) of the brain was further constructed according to the theoretical method of digital terrain analysis to realize the digital expression of the cerebral cortex morphology. The study introduced terrain factors′ indicators such as roughness, relief amplitude and elevation in geoscience to quantitatively describe the morphological characteristics of the cerebral cortex. Covariance analysis was conducted with age as the covariate, and independent sample t test was conducted with gender into groups and NC samples and AD samples as the variables, terrain factors as the group and left and right hemispheres as the variables to reveal the change rule of cerebral cortex morphology.Results·The roughness, relief amplitude and thickness of the cerebral cortex were linearly distributed with age, and the differences between the AD group and the NC group were all statistically significant (all P

Copyright of Journal of Shanghai Jiaotong University (Medical Science) is the property of Journal of Shanghai Jiaotong University (Medical Science) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Shanghai Jiaotong University (Medical Science) is the property of Journal of Shanghai Jiaotong University (Medical Science) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objective: Discuss the effect of catalpol on brain-derived neurotrophic factor (BDNF) expression in 茁-Amyloid peptide (A茁) intoxicated SH-SY5Y cells and the mechanism of regulating BDNF expression. Methods: The SH-SY5Y neuroblastoma cells induced by all-trans retinoic acid were used as the research object, and the effect of catalpol on A茁-injured cells was studied. The cell survival rate was determined by MTT assay, and the content of BDNF was determined by ELISA. The Western blot was used to detect the expression levels of transcription factors cAMP response element binding protein (CREB) and phosphorylated CREB (pCREB, activated form of CREB). The mRNA expression levels of BDNF and its series of transcripts were determined by RT-PCR. CREB expression was blocked by RNA interference and the expression of BDNF mRNA was determined by RT-PCR. Results Catalpol pre-protection increased the survival rate of SH-SY5Y cells after A茁 injury, significantly increased the content of BDNF in cell culture supernatant and intracellular BDNF mRNA level, promoted the expression of BDNF transcription factor IV and its key regulatory transcription factor pCREB. After interfered with CREB expression, the upregulation effect of catalpol on BDNF mRNA expression partially disappeared. Conclusion Catalpol may play a neuroprotective role by upregulating the phosphorylation of CREB and promoting the expression of BDNF. [ABSTRACT FROM AUTHOR]

Objective To explore expression changes of high affinity IgG receptor Fc-gamma Ⅰ type(FcγRⅠ) in brain cortex of patients with Alzheimer's disease(AD). Methods Normal human brain tissue samples and brain tissue samples with neuropathological diagnosis of AD, wild type mice and APP/PS1 mice were used. Immunofluorescence and Western blot were used to define cellular localization and expression of FcγRⅠ in cerebral cortex. Results FcγRⅠ was generally expressed in neurons of human and mouse cerebral cortex. Compared with normal human brain, FcγRⅠ expression in AD human brain cortex decreased significantly(P＜0.05). Compared with wild type mouse brain, FcγRⅠ expression in cerebral cortex of AD mouse models also decreased significantly(P＜0.05). Conclusions The expression of IgG high affinity receptor FcγRⅠ in AD human brain and cerebral cortex of AD mouse models decreases significantly that suggestes that FcγRⅠ is potentially correlated with AD neuropathological pathogenesis.

Copyright of Journal of Data Acquisition & Processing / Shu Ju Cai Ji Yu Chu Li is the property of Editorial Department of Journal of Nanjing University of Aeronautics & Astronautics and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Alzheimer's disease (AD) is a neurodegenerative disease and one of the main types of senile dementia. In recent years, abnormal mitophagy often occurs in AD patients. Relevant studies have shown that mitophagy is an important way to control the quality and quantity of mitochondria, that is, cells can remove damaged or dysfunctional mitochondria through selective autophagy to maintain the normal physiological function and energy supply. This article reviews the abnormal changes of mitophagy in AD and its role and mechanism in the occurrence and development of AD, in order to offer new ideas for controlling and delaying the process of AD by targeted induction of mitophagy. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Beijing University of Technology is the property of Journal of Beijing University of Technology, Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Alzheimer's disease (AD) is a common neurodegenerative disease. Its main pathological change is senile plaque (SP) formed by massive accumulation of amyloid β-protein (Aβ) and neurofibrillary tangles (NFTs) formed by excessive phosphorylation and accumulation of Tau protein in cells. Chaperone-mediated autophagy (CMA) selectively transfers proteins with CMA motifs to lysosomes for degradation. When the autophagy process is impaired, Aβ and abnormal phosphorylated Tau protein will accumulate in neurons, which can destroy the normal function of cells and accelerate their death. Relevant studies have shown that CMA is an important pathway for abnormal protein degradation in early AD, and the inactivation of this pathway may play an important role in the progression of AD. This paper reviews the concept, and physiological role of CMA and the pathological relationship between CMA and AD, and elaborates the role of inactivation of CMA pathway in AD diseases, in order to provide new ideas for the research and treatment of AD pathogenesis. [ABSTRACT FROM AUTHOR]

Two styryl pyrimidine derivatives substituted by p-tosyloxymethyl, Boc-SPm2-OTs and Boc-SPm5-OTs, were designed and successful synthesized, which were labeled by 18F to prepared 18F-SPm2 and 18F-SPm5 by nucleophilic substitution. The radiochemical purities of both 18F-SPm2 and 18F-SPm5 were more than 99%. Both 18F-SPm2 and 18F-SPm5 had ideal lipophilicity (LogP=1-2.5) and can maintaining stability in normal saline for over 3 h and can bind to Aβ selectively, but both 18F-SPm2 and 18F-SPm5 displayed less binding affinity (the Ki values were 246.6 nmol/L and 318.2 nmol/L, respectively). The results of biodistribution in mice demonstrated that both 18F-SPm2 and 18F-SPm5 showed relatively high initial brain uptake, with slow washout from normal brain and obvious defluorination in vivo. In conclusion, both 18F-SPm2 and 18F-SPm5 might not be ideal Aβ imaging agents, and further modifications were needed to improve the disadvantages.

Objective: To verify the relationship between β-amyloid（Aβ) plaques and glial cell activation by testing the correlation between Aβ and glial fibrillary acidic protein (GFAP) or ionized calcium binding adaptor molecule-1 (Iba-1) in the prefrontal cortex（PFC） of an Alzheimer’s Disease (AD) APPs we mouse model. Methods: Nine 12-month-old APPswe AD mice were included. The expression of Aβ, GFAP, and Iba-1 in the PFC was detected by immunohistochemistry, and the correlation of Aβ with either GFAP or Iba-1 level was analyzed. The co-existence of different sized Aβ plaques with either GFAP or Iba-1 was detected by double-immunofluorescence labeling assay. Results: Immunohistochemical results showed that higher levels of Aβ in the PFC of AD mice were associated with higher levels of GFAP and Iba-1. On the contrary, lower levels of Aβ were associated with lower levels of GFAP and Iba-1 expression. Pearson correlation analysis showed that Aβ level was positively correlated with that of GFAP（R=0.6677, P<0.05) and Iba-1（R=0.8257, P<0.05), respectively. Immunofluorescence double labeling results also demonstrated that the region with large sized Aβplaques showed a higher fluorescence signal intensity of both GFAP and Iba-1 in the PFC of AD mice when compared to that with small sized Aβ plaques. Conclusions: The level of Aβ was positively correlated with those of GFAP and Iba-1 in the PFC of AD mice, suggesting that Aβ formation plays an important role in neuroinflammation induced by the activation of glial cells. [ABSTRACT FROM AUTHOR]

Objective·To evaluate the efficacy of transcranial magnetic stimulation (TMS) on cognitive function and behavioral and psychological of dementia (BPSD) in Alzheimer′s disease (AD) patients. Methods·Nine databases including China National Knowledge Infrastructure (CNKI), WanFang, VIP, Chinese Biomedical Literature Database (CBM), PubMed, Embase, the Cochrane Library and Chinese and American Clinical Trial Center were searched before November 2, 2019. English was searched with the topics of "Alzheimer′s disease" "transcranial magnetic stimulation" and "randomize controlled trial", and free words were retrieved. Chinese was searched with the topics of"阿尔茨海默病""经颅磁刺激""随机对照试验". According to the pre-established inclusion and exclusion criteria, the literatures were screened. RevMan 5.3 software was used. The standardized mean difference (SMD) was used as the effect value, and 95% confidence interval (CI) was used for interval estimation. Gradeprofile 3.2.2 software was used to evaluate the quality of evidence. Results·A total of 23 articles were included. In improving cognitive function, the evaluation results of AD Assessment Scale-Cognitive suggest that SMD of high frequency TMS group was -0.64 (95%CI -0.89 ‒ -0.40, P=0.000), SMD of low frequency TMS group was -0.58 (95%CI -1.12 ‒ -0.05, P=0.030). The Grade of evidence quality was very lower and lower respectively. When using Mini-Mental State Examination to evaluate cognitive function, it was divided into three subgroups according to TMS frequency (high or low, value) and treatment times. The results showed that SMD in high frequency TMS group was 1.30 (95% CI 0.76‒1.85, P = 0.000), but no significant difference was found in low frequency group. The Grade of evidence quality were both very lower. In 5 Hz group, SMD was 3.99 (95%CI 0.81~7.16, P=0.010) and the Grade evidence quality grade was very low. In the group of treatment times >40 and ≤60, SMD was 3.28 (95%CI 1.67‒4.90, P=0.000) and the Grade evidence quality grade was very low. In the aspect of improving BPSD, the Neuropsychiatric Inventory was used to evaluate, and the result was no statistically significant. The Grade evidence quality grade was very low. Behavioral Pathology in Alzheimer′s Disease Scale showed that SMD of high frequency group was -0.83 (95%CI -1.06‒ - 0.60, P=0.000), and there was no significance in low frequency group. The Grade evidence quality grade were low and very low respectively. Conclusion·TMS could improve the cognitive function of patients with AD, and high frequency was better than low frequency. The quality of evidence was lower. Whether the BPSD of AD patients were effective needs further research. In the future, more high-quality clinical multicenter randomized controlled trails should be included to study the efficacy and safety of TMS in the treatment of AD, so as to provide guidance for clinical practice. [ABSTRACT FROM AUTHOR]

Objective • To explore whether different test indicators and observation periods in contextual fear conditioning test affect the detection effectiveness of learning and memory ability of 5XFAD transgenic mice. Methods - Twelve 4-month-old female 5XFAD transgenic progeny mice and 14 4-month-old female LM progeny mice were selected, which were produced by crossing male SXFAD transgenic mice and female C57BL/6 mice, to conduct open field test and contextual fear conditioning test in succession. Total distance and velocity in open field test and average motion index in the firet 60 s of training stage in contextual fear conditionii堪 test of the two groins of mice were used to evaluate the difference of locomotor activity. Besides, the first 180 s, 181--360 s and the first 300 s of testing stage for observation were selected to evaluate the selection effects on percent freeze and activity suppression ratio. Then further investigation was launched to e冲lore the effects of different observation periods on the detection effectiveness of percent freeze and activity suppression ratio. Results* The differences of total distance and total velocity of the two groups of mice in open field test were not statistically significant however the average motion index in the first 60 s of training stage in contextual fear conditioning test of SXFAD transgenic mice was significantly higher than that of LM mice (7M).O27), The comparison of percent freeze among the three groups of observation periods of LM mice had significant difference (both P<0.05)，while there was no statistical significance in activity suppression ratio. The comparisons of percent freeze and activity suppression ratio among the three groups of observation periods of 5XFAD mice had no significant difference. The differences of percent freeze between SXFAD mice and LM mice was not statistically significant during the three observation periods. However, the activity suppression ratio of 5XFAD mice was significantly higher than that of LM mice in the first 180 s (7MX038), in the other two observation periods the difiference of activity suppression ratio between the two groups of mice was not statistically significant Conclusionv The average motion index detected in training stage in contextual fear conditioning test is more sensitive than total distance and total velocity detected in open field test for evaluating locomotor activity of SXFAD mice. In contextual fear conditioning test, different observation periods have effects oil the value of percent freeze provided by single strain of mice, while the value of activity suppression ratio remains unaffectei Activity suppression ratio is more precise than percent fteezeto reflect the cognitive deficiency of 5XFAD mice. It is more accurate to select the first 180 s of testing stage for observatioa. [ABSTRACT FROM AUTHOR]

Objectives: To compare the effects of pressing moxibustion at Baihui (GV 20) and Guanyuan (CV 4) combined with donepezil hydrochloride tablets and donepezil hydrochloride tablets alone on cognitive impairment in patients with mild to moderate Alzheimer's disease(AD), and to explore the mechanism of pressing moxibustion in the treatment of mild to moderate AD from the serum levels of β-amyloid 1-42 (Aβ 1-42 ), microtubule-associated protein tau and phosphorylated tau (P-tau)., Methods: A total of 76 patients with mild to moderate AD were randomly divided into an observation group (38 cases, 4 cases dropped out) and a control group (38 cases, 2 cases dropped out). Patients in the control group were given oral donepezil hydrochloride tablets (5 mg each time, once a day). On the basis of the control group, patients in the observation group were treated with pressing moxibustion at Baihui (GV 20) and Guanyuan (CV 4), 5 cones per acupoint, once every other day, three times a week. Both groups were treated for 8 weeks. The scores of mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were compared between the two groups before treatment, after treatment and after 4 and 12 weeks of treatment completion. The serum levels of Aβ 1-42 , tau and P-tau were detected before and after treatment in the two groups, and the safety was evaluated., Results: At each time point after treatment, the MMSE and MoCA scores of the two groups were higher than those before treatment ( P <0.05), and the scores in the observation group were higher than those in the control group ( P <0.05). After treatment, the serum levels of Aβ 1-42 , tau and P-tau in the two groups were lower than those before treatment ( P <0.05), and above indexes in the observation group were lower than those in the control group ( P <0.05). There was no significant difference in the safety level between the two groups ( P >0.05)., Conclusions: The short-term and long-term effect of pressing moxibustion at Baihui (GV 20) and Guanyuan (CV 4) combined with donepezil hydrochloride tablets in improving cognitive impairment in mild to moderate AD is better than that of donepezil hydrochloride tablets alone, and can reduce serum levels of Aβ 1-42 , tau and P-tau, which may be one of the mechanisms of pressing moxibustion to improve cognitive impairment.

Objective To observe the neuroprotective effect of herbal medicine Gengnianchun formula (GNC) on primary cultured rat fetal hippocampal neurons injury induced by amyloid beta 25-35 fragment (Aβ25-35)through ERβ and PI3K/Akt signaling pathway. Methods Human neuroblastoma cell line (SH-SY5Y) were treated with Aβ25-35 to establish an in vitro cell model of Alzheimer's disease (AD) and were cultured with different concentration of GNC serum (GS) and Aβ25-35 to determine the appropriate treatment concentration and duration of these drugs by cell viability test (CCK-8) method. Primary cultured rat fetal hippocampal neurons were treated with Aβ25-35 to establish an in vitro cell model of AD and were divided into 5 groups,including control group,model group,GS group,normal saline serum(NS) group and PHTPP(a selective ERβ antagonist) group. Morphological observation,CCK-8 test and LDH release assay were used to evaluate the cell injury of primary cultured rat fetal hippocampal neurons. Hoest33258/PI double fluorescence staining,qRT-PCT and Western blot experiments were used to evaluate the cell apoptosis of primary cultured rat fetal hippocampal neurons. Results Compared with the control group,synaptic shrink,collapse and cell debris of primary cultured rat fetal hippocampal neurons were more obvious,cell viability decreased and LDH release increased in model group. Compared with the model group and NS group,synaptic shrink,collapse and cell debris of primary cultured rat fetal hippocampal neurons reduced,cell viability increased,LDH release decreased,number of PI positive primary cultured rat fetal hippocampal neurons were decreased,levels of bax/bcl-2 and cyt-c mRNA and the protein levels of bax/bcl-2,cleaved-caspase-3 and cyt-c were down-regulated and level of p-Akt was up-regulated in GS group. Compared with GS group,levels of bax/bcl-2 and cyt-c mRNA and the protein levels of bax/bcl-2,cleaved-caspase-3 and cyt-c were up-regulated and level of p-Akt was down-regulated in PHTPP group.Conclusions Neuroprotective effect of GNC on primary cultured rat fetal hippocampal neurons injury was mediated by or at least partly by ERβ and PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Beijing University of Technology is the property of Journal of Beijing University of Technology, Editorial Department and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

With the improvement of quality of life, the life expectancy of residents is generally prolonged, and people suffering from Alzheimer's disease (AD) is increasing. Epidemiological and animal experiments have found that atmospheric particulate matter is associated with AD. This article briefly reviews the mechanisms of AD-related oxidative stress damage and neuroinflammation caused by atmospheric fine particulate matter entering the brain via olfactory bulb pathway. [ABSTRACT FROM AUTHOR]

Objective To explore the protective effects of butylphthalide against Aβ25-35 induced dementia-like pathological rat model and reveal the mechanism. Methods Rats were divided into five groups: control group, model group and NBP groups (10, 30, and 100mg/kg). In model group and butylphthalide groups, Aβ25-35 was injected into the lateral ventricle, while the rats in intervention group were administered with butylphthalide (gastric infusion dose of 2.5mL/kg). Learning and memory abilities of the rats were observed with water maze test. Mitochondrial function in brain tissue was observed by ATP assay, and the mitochondrial related enzyme activities were detected by the kit. Results Water maze test showed that learning and memory abilities of model group were poorer than those of control group. They were significantly improved in NBP 10mg/kg group and 30mg/kg group (P<0.05), but did not change significantly in 100mg/kg group. Compared with control group, model group had significantly decreased ATP level (P<0.05); cytochrome c oxidase, pyruvate dehydrogenase complex and ketoglutarate dehydrogenase activities were also significantly decreased (P<0.05). Compared with model group, butylphthalide group had significantly improved activities of mitochondrial enzymes that improved mitochondrial function. Conclusion Butylphthalide can improve learning and memory abilities of rats with Aβ25-35-induced dementia by improving mitochondrial function. [ABSTRACT FROM AUTHOR]

Objective: To investigate the roles of S100B protein and anti-brain antibody (ABAb) in the pathophysiology of Alzheimer's disease (AD) by analyzing the changes of the serum levels of S100B and ABAb and the relationships of the measures with cognition deficits in patients with AD. Methods: In this study, 32 patients with AD(AD group) and 40 age-matched volunteers without cognitive impairment (control group) were enrolled. The diagnosis was made according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSMIV). The mental and social functional conditions were assessed with the Mini-Mental State Examination (MMSE) and Activity of Daily Living Scale (ADL). the cognitive function of patients was evaluated with the Alzheimer's Disease Assessment Scale-cognitive subscale(ADAS-Cog). The serum S100B proteinand ABAb levels were examined by enzyme-linked immuno sorbent assay (ELISA). Results: The serum S100B protein [ (0. 66 ±0. 17) )μg/L vs. (0. 30 ±0. 04)/μg/L] and ABAb [(1.93 ± 0.95) U/L vs. (1.31 ± 0.25) U/L] levels were higher in AD patients than in the controls (P s < 0.01). In AD patients, the serum S100B protein markedly negatively correlated with the scores of the MMSE(r = - 0. 66), while positively correlated with ADL and ADAS-Cog(r =0. 57, r =0. 53) (Ps <0. 005). ABAb levels negatively correlated with the scores of the MMSE(r = - 0 . 57), while positively correlated with ADL and ADAS-Cog(r =0. 52, r =0. 34))Ps <0. 05). The serum S100B protein levels were positively related to ABAb levels in AD group(r = 0. 51, P < 0. 005), but not in control group(r =0. 076, P =0. 654). Conclusions: It suggests that the serum levels of S100B protein and ABAb are related with cognitive function in patients with Alzheimer's disease, and S100B protein and ABAb might play key roles in mechanism of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate the correlation between the Alzheimer's disease (AD) and the changes in promoter regions of progranulin (PGRN) and tumor necrosis factor receptor (TNFR) and the whole genome DNA methylation status. Methods: Eighty blood specimen were collected from Alzheimer's disease patients and another eighty blood specimen were collected from healthy people. The promoter regions of PGRN and TNFR were amplified by Polymerase chain reaction (PCR) and were sequenced to detect the difference of the sequence variations (SNPs) in two groups. At the same time. DNA methylation levels in PGRN and TNFR promoter regions and in whole genome were detected with methlation specific PCR and ELISA respectively. Results: Significant differences were found in rs4149570 and rs4149569 located in promoter regions of TNFR in patients compared to control group (P<0.001 and P=0.033). The whole genome methylation level was (0.79± 0.29)% in Alzheimer's disease group and lower than those in control group (1.00± 0.36)% (P< 0.001). Conclusion: TNFR promoter gene rs4149570 and rs4149569 variants and the decrease of whole genome DNA methylation were related to AD. [ABSTRACT FROM AUTHOR]

Objective To establish the rat model of type 2 diabetes mellitus (T2DM)-induced Alzheimer’s disease (AD). Methods The rat model of T2DM was established by continuous high fat and high glucose diet in aged rats. Then the rat model was screened and identified by using Morris water maze, cerebrospinal fluid microdialysis technique, ELISA, electrophysiological technique and pathologic method, respectively. Results Compared with the normal group and the T2DM group, the rats in T2DM+DM group had obviously learning and memory impairment; the level of β-AP in the hippocampus was significantly higher and the frequency of the spikes induced by Achin the hippocampus was notably lower. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenera-tire disease and the most common form of dementia．There is the heavy burden to families and society with the growing number of AD patients, which forces us further to explore the mechanism of Alzheimer's disease (AD). Among the pathogenesis of AD, the tau protein hypothesis is more popular. The microtubule associated protein -tau, with its abnormal phosphorylation structure by forming dimers, oligomers and neurofibrillary tangles, involves in the pathological process of AD, under the interaction of proteases and regulatory proteins including protein phosphatase 2A (PP2A), glycogen synthase kinase 3-β (GSK - 3β), cell cycle dependent protein kinase 5 (CDK - 5) and the Bcl - 2. Tau and its related structure may either start or promote the apoptosis of AD or inhibit the acute apoptosis but contribute to the chronic nerve cell degeneration. Uncover the mystery, may uncover the mysteries of pathological changes of AD. [ABSTRACT FROM AUTHOR]

Objective To investigate whether astaxanthin (ATX) has neuroprotective effects against Aβ25-35-induced neurotoxicity through inhibiting MAPK activation. Methods Cultured SH-SY5Y cells were treated with Aβ25-35 preincubated with or without ATX. Cell viability was determined and intracellular reactive oxygen species (ROS) level was measured by fluorescence microplate reader. The expressions of pJNK and pp38MAPK were assayed by Western blot. Results Pre-treatment with ATX for 4h significantly reduced the Aβ25-35-induced viability loss (P<0.01). Pre-treatment with ATX attenuated Aβ25-35-mediated ROS production. The viability of SH-SY5Y cells was significantly increased in Aβ+ATX group (P<0.01) and ROS production was decreased. In addition, Aβ activated JNK and p38MAPK, but ATX pre-treatment inhibited Aβ25-35-induced expression of JNK and p38MAPK. Conclusion ATX has neuroprotective effects against Aβ25-35-induced neurotoxicity through JNK and p38MAPK pathways. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of moxibustion on autophagy and amyloid β-peptide 1-42 (Aβ 1-42 ) protein expression in amyloid precursor protein/presenilin 1 (APP/PS1) double-transgenic mice with Alzheimer's disease (AD)., Methods: After 2-month adaptive feeding, fifty-six 6-month-old APP/PS1 double transgenic AD mice were randomly divided into a model group, a moxibustion group, a rapamycin group and an inhibitor group, 14 mice in each group. Another 14 C57BL/6J mice with the same age were used as a normal group. The mice in the moxibustion group were treated with monkshood cake-separated moxibustion at "Baihui"(GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14) for 20 min; the mice in the rapamycin group were intraperitoneally injected with rapamycin (2 mg/kg); the mice in the inhibitor group were treated with moxibustion and injection of 1.5 mg/kg 3-methyladenine (3-MA). All the treatments were given once a day for consecutive 2 weeks. The morphology of hippocampal tissue was observed by HE staining; the ultrastructure of hippocampal tissue was observed by transmission electron microscopy; the expression of Aβ 1-42 protein in frontal cortex and hippocampal tissue was detected by immunohistochemistry; the expressions of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), p70 ribosomal protein S6 kinase (p70S6K) and phosphorylated p70S6K (p-p70S6K) protein in hippocampus were detected by Western blot method., Results: Compared with the normal group, the number of neuron cells was decreased, cells were necrotic and deformed, and autophagy vesicle and lysosome were decreased in the model group. Compared with the model group, the number of neuron cells was increased, cell necrosis was decreased, and autophagy vesicle and lysosome were increased in the moxibustion group and the rapamycin group. Compared with the normal group, the protein expressions of Aβ 1-42 , mTOR, p-mTOR, p70S6K and p-p70S6K in the model group were increased ( P <0.05); compared with the model group, the protein expressions of Aβ 1-42 , mTOR, p-mTOR, p70S6K and p-p70S6K in the moxibustion group, rapamycin group and inhibitor group were decreased ( P <0.05); compared with the inhibitor group, the protein expressions of Aβ 1-42 , mTOR, p-mTOR, p70S6K and p-p70S6K in the moxibustion group and rapamycin group were decreased ( P <0.05); compared with the rapamycin group, the protein expressions of mTOR, p-mTOR, p70S6K and p-p70S6K in the moxibustion group were decreased ( P <0.05)., Conclusion: Moxibustion could enhance autophagy in hippocampal tissue of APP/PS1 double transgenic AD mice and reduce abnormal Aβ aggregation in brain tissue, the mechanism may be related to the inhibition of mTOR/p70S6K signaling pathway.

Objective: To observe the clinical effect of moxibustion with deqi on Alzheimer's disease (AD) rats, and evaluate its effect on β-amyloid (Aβ) transport and enzymatic degradation proteins, to explore its molecular mechanism for improving cognitive function., Methods: Sixty SPF-grade male SD rats were randomly divided into a blank group (8 rats), a sham-operation group (8 rats) and a model establishment group (44 rats). The rats in the model establishment group were injected with Aβ 1 - 42 at bilateral ventricles to establish AD model. Among the 38 rats with successful model establishment, 8 rats were randomly selected as the model group, and the remaining rats were treated with mild moxibustion at "Dazhui" (GV 14), once a day, 40 min each time, for 28 days. According to whether deqi appeared and the occurrence time of deqi , the rats were divided into a deqi group (12 rats), a delayed deqi group (10 rats) and a non-deqi group (8 rats). After the intervention, the Morris water maze test was applied to evaluate the cognitive function; the HE staining was applied to observe the brain morphology; the Western blot method was applied to measure the protein expression of Aβ and its receptor mediated transport [low-density lipoprotein receptor-related protein (LRP) 1, receptor for advanced glycation end products (RAGE), apolipoprotein E (ApoE)] and enzymatic degradation [neprilysin (NEP), insulin degrading enzyme (IDE), endothelin converting enzyme (ECE)-1 and angiotensin converting enzyme (ACE) 2]., Results: Compared with the sham-operation group, in the model group, the escape latency was prolonged ( P <0.01), and the times of platform crossing and the ratio of platform quadrant to total time were reduced ( P <0.01); the brain tissue was seriously damaged; the expression of hippocampal Aβ and RAGE was increased ( P <0.01), and the expression of hippocampal LRP1, ApoE, NEP, IDE, ECE-1 and ACE2 was decreased ( P <0.01). Compared with the model group, the escape latency was shortened in the deqi group ( P <0.05, P <0.01), and the escape latency in the delayed deqi group and the non-deqi group was shortened from Day 2 to Day 5 ( P <0.05, P <0.01), and the times of platform crossing and the ratio of platform quadrant to total time were increased in the deqi group and the delayed deqi group ( P <0.01, P <0.05); the brain damage in each moxibustion group was reduced, which was smallest in the deqi group, followed by the delayed deqi group and the non-deqi group; the expression of Aβ and RAGE was decreased ( P <0.01, P <0.05) and the expression of LRP1 and IDE was increased in each moxibustion group ( P <0.01, P <0.05); the expression of ApoE was increased in the deqi group and the delayed deqi group ( P <0.01, P <0.05); the expression of NEP was increased in deqi group ( P <0.05), and the expression of ECE-1 and ACE2 was increased in the deqi group and the delayed deqi group ( P <0.05). Compared with the delayed deqi group and the non-deqi group, the escape latency in the deqi group was shortened from Day 3 to Day 5 ( P <0.05), and the times of platform crossing and the ratio of platform quadrant to total time were increased ( P <0.05, P <0.01). Compared with the non-deqi group, the expression of Aβ was reduced ( P <0.05), the expression of LRP1 and ApoE was increased in the deqi group ( P <0.05). The expression of NEP in the deqi group was higher than that in the delayed deqi group and the non-deqi group ( P <0.05)., Conclusion: Compared with non- deqi , moxibustion with deqi could promote Aβ transport and degradation, thereby reducing Aβ level in the brain and improving cognitive function for AD rats.

Objective: To compare the clinical efficacy of abdominal acupoint thread embedding therapy based on "brain-intestinal connection" combined with donepezil hydrochloride tablets and oral donepezil hydrochloride tablets alone for mild-to-moderate Alzheimer's disease (AD) and observe its effects on amyloid precursor protein (APP) and β-amyloid protein 1-42 (Aβ 1-42 )., Methods: Sixty patients with AD were randomly divided into an observation group (30 cases, 3 cases dropped off) and a control group (30 cases, 3 cases dropped off). The patients in the control group were treated with donepezil hydrochloride tablets (5 mg per day); based on the treatment in the control group, the patients in the observation group were treated with abdominal acupoint thread embedding therapy at Zhongwan (CV 12), Xiawan (CV 10), Huaroumen (ST 24), Wailing (ST 26), Daheng (SP 15), etc., once every 10 days. Both groups were treated for 2 months. The mini-mental state examination (MMSE), Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog), activity of daily living scale (ADL), neuropsychiatric inventory questionnaire (NPI) as well as the serum levels of APP and Aβ 1-42 were observed before and after treatment in the two groups., Results: After treatment, the MMSE scores in the two groups were higher than those before treatment ( P <0.05), and the ADAS-Cog, ADL and NPI scores were lower than those before treatment ( P <0.05). After treatment, the MMSE score in the observation group was higher than that in the control group ( P <0.05), and the ADAS-Cog, ADL and NPI scores were lower than those in the control group ( P <0.05). After treatment, the serum levels of APP and Aβ 1-42 were lower than those before treatment ( P <0.05), and the serum levels of APP and Aβ 1-42 in the observation group was lower than those in the control group ( P <0.05)., Conclusion: The abdominal acupoint thread embedding therapy based on the theory of "brain-intestinal connection" combined with donepezil hydrochloride tablets can improve cognitive function, self-care ability of daily life and mental behavior, and reduce the serum levels of APP and Aβ 1-42 in patients with mild-to-moderate AD, which have superior clinical effect to donepezil hydrochloride tablets alone.

Objective: To observe the effect of electroacupuncture (EA) on the expression of insulin phosphatidylinositol-3 kinase/glycogen synthetase kinase-3α (PI3K/GSK3α) signal pathway related proteins in the hippocampus in mice with Alzheimer's disease (AD), and to explore the regulatory mechanism of EA on improving the pathological characteristics of AD., Methods: Twelve male APP/PS1 double transgenic mice were randomly divided a model group and a treatment group, 6 mice in each group; another 6 wild-type male mice were taken as the control group. The mice in the treatment group were treated with EA (continuous wave, 2 Hz of frequency) at "Baihui" (GV 20) and bilateral "Shenshu" (BL 23), once a day; 7-day treatment was taken as a course of treatment, and 2 courses of treatment were given. The immunohistochemistry method and Western blot method were used to detect the distribution and expression level of hippocampal PI3K/GSK3α signal pathway related proteins P85α, P110α, GSK3α and pS 21 GSK3α, and the number of hippocampal senile plaques (SP) was observed., Results: The proteins of P85α, P110α, GSK3α and pS 21 GSK3α were mainly distributed in the cytoplasm of hippocampal neurons, and the GSK3α was also distributed in the axons of neurons in the model group and the treatment group. The immunohistochemistry results showed that the distribution level of GSK3α in the hippocampus in the model group was significantly higher than that in the control group ( P <0.001), and the distribution level of pS 21 GSK3α, P85α and P110α was significantly decreased ( P <0.01, P <0.001); compared with the model group, the distribution level of GSK3α in the hippocampus in the treatment group was significantly decreased ( P <0.001), and the distribution level of pS 21 GSK3α, P85α and P110α in hippocampus was significantly increased ( P <0.05, P <0.001). The Western blot results showed compared with the control group, the expression of pS 21 GSK3α, P85α and P110α as well as the ratio of pS 21 GSK3α/GSK3α in the hippocampus in the model group were significantly decreased ( P <0.001), and the expression of GSK3α was increased ( P <0.05); compared with the model group, the expression of pS 21 GSK3α, P85α, P110α and the ratio of pS 21 GSK3α/GSK3α in the hippocampus in the treatment group were significantly increased ( P <0.01, P <0.001), and the expression of GSK3α was decreased ( P <0.05). Compared with the control group, the number of hippocampal SP in the model group was significantly increased ( P <0.001); compared with the model group, the number of hippocampal SP in the treatment group was significantly decreased ( P <0.01)., Conclusion: EA could effectively regulate the expression of PI3K/GSK3α signal pathway related proteins in the hippocampus in mice with AD, so as to reduce the formation and deposition of SP.

Objective: To compare the therapeutic effect of electroacupuncture (EA) combined with donepezil hydrochloride and donepezil hydrochloride alone on improving learning-memory ability in patients with Alzheimer's disease (AD), and to explore its action mechanism., Methods: Sixty patients of AD were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the observation group were treated with EA at governor vessel (GV) combined with donepezil hydrochloride. EA was applied at Baihui (GV 20) and Fengfu (GV 16) with dilatational wave (10 Hz/50 Hz of frequency, 0.5 to 5.0 mA of intensity), and the needles were kept for 40 min, EA was given once a day; the donepezil hydrochloride tablet was taken orally, 5 mg, once a day, and after 4 weeks the dosage might be increased to 10 mg per day according to the specific situation. All the treatment was given for 8 weeks. The patients in the control group were only treated with donepezil hydrochloride with the identical procedure as the observation group. The Montreal cognitive assessment (MoCA) and Alzheimer's disease assessment scale cognitive part (ADAS-Cog) were evaluated before and after treatment; P300 (latency and amplitude of N2 and P3) was detected by EEG/ERP system brain event related potential instrument, and amyloid precursor protein (APP) and β-amyloid protein 1-42 (Aβ 1-42 ) were detected by ELISA., Results: Compared before treatment, the MoCA scores were increased after treatment in the two groups ( P <0.05), and the MoCA score in the observation group was higher than that in the control group ( P <0.05). Compared before treatment, the ADAS-Cog scores were decreased after treatment in the two groups ( P <0.05), and the ADAS-Cog score in the observation group was lower than that in the control group ( P <0.05). Compared before treatment, the latency of N2 and P3 was shortened and the amplitude was increased after treatment in the two groups ( P <0.05); after treatment, the latency of N2 and P3 in the observation group was shorter than that in the control group and the amplitude was higher than that in the control group ( P <0.05). Compared before treatment, the serum levels of APP and Aβ 1-42 were lower after treatment in the two groups ( P <0.05), and the serum levels of APP and Aβ 1-42 in the observation group were lower than those in the control group ( P <0.05)., Conclusion: EA at Baihui (GV 20) and Fengfu (GV 6) combined with donepezil hydrochloride can effectively reduce the serum levels of APP and Aβ 1-42 and improve the scores of MoCA and ADAS-Cog and the levels of N2 and P3 of P300 in AD patients, which has superior effect to donepezil hydrochloride alone in improving the learning-memory of AD patients.

Objective: To explore the effect of early intervention electroacupuncture (EA) at "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenshu" (BL 23) on the learning-memory ability and the expression of phosphorylated Tau protein in the hippocampus of SAMP8 mice, so as to provide reference for the intervening period of EA for Alzheimer's disease (AD)., Methods: A total of 36 3-month old SAMP8 mice were randomly divided into a model group, a 3-month-old EA group and a 9-month-old EA group, 12 mice in each group. Twelve normal SAMR1 mice with the same age were taken as the control group. The mice in the 3-month-old EA group and 9-month-old EA group were treated with EA at "Baihui" (GV 20), "Dazhui" (GV 14) and "Shenshu" (BL 23) separately 3 months old and 9 months old (continuous wave, 2 Hz, 1.5-2 mA), 20 min each time, once a day, 8 days as a course of treatment, with an interval of 2 days between courses, totally 3 courses of treatment were given. The mice sample in each group was collected at the age of 10 months after the learning-memory ability tested by Morris water maze. The expression of phosphorylated Tau protein in the hippocampus was detected by immunohistochemistry and Western blot, and the expression of Tau mRNA was detected by real-time PCR., Results: Compared with the control group, in the model group, the escape latency was significantly increased ( P <0.01), the time of stay in the original platform quadrant and the number of crossing the platform quadrant were reduced ( P <0.01), and the expressions of phosphorylated Tau protein and Tau mRNA in hippocampus were increased ( P <0.01). Compared with the model group, in the 3-month-old EA group and 9-month-old EA group, the escape latency was significantly reduced ( P <0.05), the time of stay in the original platform quadrant and the number of crossing the platform quadrant were increased ( P <0.05), and the expressions of phosphorylated Tau protein and Tau mRNA in hippocampus were reduced ( P <0.05). Compared with the 9-month-old EA group, in the 3-month-old EA group, the escape latency was significantly reduced ( P <0.05), the time of stay in the original platform quadrant and the number of crossing the platform quadrant were increased ( P <0.05), and the expressions of phosphorylated Tau protein and Tau mRNA were reduced ( P <0.01)., Conclusion: The early EA intervention could more effectively improve the learning-memory ability and inhibit phosphorylation of Tau protein in the hippocampus of SAMP8 mice.

Objective: To explore the mechanism of acupuncture plus medication on treatment of Alzheimer's disease (AD)., Methods: Sixty adult SD rats were randomly divided into a normal group, a sham operation group, a model group, an electroacupuncture (EA) group, a gastrodin group and an EA+gastrodin group, 10 rats in each one. The rat model of AD was established by intraperitoneal injection of D-galactose and bilateral hippocampal injection of Aβ1-40. Two weeks after modeling, the rats in the EA group and EA+gastrodin group were treated with EA at "Baihui" (GV 20) "Dazhui" (GV 14) and bilateral "Zusanli" (ST 36), 30 min per treatment, once a day for consecutive 4 weeks. The rats in the gastrodin group and EA+gastrodin group were treated with intraperitoneal injection of gastrodin, once a day for consecutive 4 weeks. The rats in the normal group, model group and sham operation group were not treated. The morphology of hippocampal neurons was observed by using HE staining. The expression of Bcl-2 and Bax in the hippocampal CA1 area was detected by using immunohistochemical method. The expression of Bcl-2 and Bax protein in hippocampus was detected by using Western blot., Results: The HE staining results showed the arrangement of neurons in the hippocampal CA1 area was regular in the normal group and the sham operation group, and the cytoplasm and nucleus were clearly visible. The neurons in the model group were severely damaged; the cell arrangement was not close, and the cell morphology was incomplete. Compared with the model group, the cell morphology of each intervention group was significantly improved. The immunohistochemistry results showed that, compared with the normal group and the sham operation group, the expression of Bcl-2 in the hippocampal CA1 region in the model group was decreased ( P <0.05), but the expression of Bax was enhanced ( P <0.05); compared with the model group, the expression of Bcl-2 was increased (all P <0.05) and the expression of Bax was decreased (all P <0.05) in all intervention group; compared with the EA group or the gastrodin group, the expression of Bcl-2 was enhanced ( P <0.05) and the expression of Bax was decreased ( P <0.05) in the EA+gastrodin group. The result of Western blot method was consistent with that of immunohistochemistry method., Conclusion: EA and gastrodin could significantly inhibit the expression of Bax and up-regulate the expression of Bcl-2, and the combination of EA and gastrodin has the most significant effect. This indicates that EA combined with gastrodin has synergistic effect on inhibiting the apoptosis of neurons in hippocampus in AD rats, which may be one of the mechanisms of EA plus medication on AD lesions.

Objective: To observe the efficacy and safety of electroacupuncture (EA) on improving mini-mental state examination (MMSE) in patients with Alzheimer's disease (AD), and to evaluate the efficacy during follow-up visit., Methods: Forty patients were randomly divided into a treatment group and a control group, 20 patients in each one (3 patients dropped off in the treatment group and 4 patients in the control group). The patients in the treatment group were treated with acupuncture at Baihui (GV 20), Fengfu (GV 16), Shenting (GV 24), Taiyang (EX-HN 5), Shangyintang (Extra 3) and Dazhong (KI 14); besides, EA was applied at Taiyang (EX-HN 5), Baihui (GV 20) and Shenting (GV 24) with dilatational wave, 10 Hz/50 Hz in frequency, 0.5 to 5.0 mA in intensity, once every two days, three treatments per week. The patients in the control group were treated with oral administration of donepezil hydrochloride tablets, once a day, taken before sleep. The treatment was given for 12 weeks in the two groups. The MMSE was evaluated before treatment, 12 weeks±3 days into treatment, and 24 weeks±7 days after treatment, respectively., Results: The difference of total score of MMSE before and 12 weeks±3 days into treatment was not significant between the two groups ( P >0.05); the total score of MMSE after treatment was higher than that before treatment (both P <0.05); compared before treatment, the short-term memory score was increased in the treatment group ( P <0.05), and the increasing range was superior to that in the control group ( P <0.05). Compared before treatment, the total score of MMSE in the two groups were reduced 24 weeks ±7 days after treatment (both P <0.05), and the reduction in the treatment group was less than that in the control group ( P <0.05); the differences of short-term memory score before and after treatment was significant between the two groups ( P <0.05). No adverse reaction occurred in the two groups., Conclusion: The effect of EA on improving MMSE in patients with AD is similar to donepezil supported by evidence-based medicine. The effect of EA may have a certain continuous effect, and may have advantages in instantaneous memory. In addition, the EA is safe.

Objective: To investigate the effects of adiponectin (APN) on anxiety and memory impairment of 9-month-old triple transgenic Alzheimer's disease (3xTg-AD) model mice., Methods: The 9-month-old 3xTg-AD mice and C57BL/6J mice were randomly divided into four groups ( n =8 for each group):Wild type(WT)+Saline, 3xTg-AD +Saline, WT+APN and 3xTg-AD +APN group. All mice were implanted cannula in lateral ventricle and each mouse was intracerebroventricular injected with adiponectin or saline under free moving condition after 7 days recovery. The anxiety and memory ability of each mouse were observed by using open field test, object recognition task and Y-maze test., Results: ①In the open field test, compared to WT+Saline group, the time of 3xTg-AD +Saline mice spent in center was significantly decreased, and the time spent in periphery was obviously increased. However, APN treatment effectively reversed the phenomenon appeared in 3xTg-AD mice, indicating that APN could alleviate the anxiety observed in 3xTg-AD mice. ②In novel object recognition task, the discrimination index of 3xTg-AD+Saline group was (-16.7±10.1)%, significantly lower than (18.0±8.2)% in WT+Saline group ( P <0.01) and (15.7±8.8)% in 3xTg-AD+APN group ( P <0.01), which indicated that APN could effectively prevent the recognition memory impairment in 3xTg mice. ③In Y-maze test, the spontaneous alternation rate of 3xTg-AD +Saline group was (40.0±1.7)%,significantly lower than (56.6±4.6)% in WT+Saline group and (53.9±5.6)% in 3xTg-AD +APN group ( P <0.01), which indicated that APN could prevent working memory impairment in 3xTg-AD mice., Conclusions: Adiponectin could effectively alleviate the anxiety and reverse the impairment of recognition memory and working memory of 9-month-old 3xTg-AD mice, and might play an important role in the prevention and treatment of AD.