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Is Alzheimer’s Disease Transmissible in Humans?

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Neuroscience bulletin 2019年第6期35卷 1113-1115页

作者： Xian-le Bu Wei-Wei Li Yan-Jiang Wang Department of Neurology and Centre for Clinical Neuroscience Daping Hospital Third Military Medical University

Alzheimer’s disease(AD),the most common type of dementia,has been identified as a protein misfolding disease with the accumulation of abnormally folded amyloid-β(Aβ)protein and hyperphosphorylated tau protein in the brain[1,2].Aβ is known to play a crucial role in the pathogenesis of AD.Deposition of Aβ protein in the brain parenchyma causing senile plaques is the obligatory event in AD pathogenesis.Aβ protein is also deposited in the media and adventitia of small and midsized cerebral arteries leading to cerebral amyloid angiopathy(CAA),which is also present in the large majority of AD patents.

关键词： Alzheimer Aβ tau

Parabiosis modeling:protocol,application and perspectives

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Zoological Research 2021年第3期42卷 253-261页

作者： Cui Yang Zhi-Lan Liu Jun Wang Xian-le Bu Yan-Jiang Wang Yang xiang Institute of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital ChengduSichuan 610072China Department of Neurology General Hospital of Western Theater CommandChengduSichuan 610083China Department of Neurology and Center for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing 400012China Department of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China

Parabiosis is a surgical method of animal modeling with a long history.It has been widely used in medical research,particularly in the fields of aging,stem cells,neuroscience,and immunity in the past two decades.The protocols for parabiosis have been improved many times and are now widely accepted.However,researchers need to consider many details,from surgical operation to perioperative management,to reduce mortality and maintain the parabiosis union.Although parabiosis has certain inevitable limitations,it still has broad application prospects as an irreplaceable animal model in the medical research field.

关键词： Parabiosis Application Protocols Surgical technique Perioperative management

Polysaccharide Krestin Prevents Alzheimer’s Disease-type Pathology and Cognitive Deficits by Enhancing Monocyte Amyloid-βProcessing

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Neuroscience bulletin 2022年第3期38卷 290-302页

作者： Si-Han Chen Chen-Yang He Ying-Ying Shen Gui-Hua Zeng Ding-Yuan Tian Yuan Cheng Man-Yu Xu Dong-Yu Fan Cheng-Rong Tan An-Yu Shi Xian-le Bu Yan-Jiang Wang Department of Neurology and Centre for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing400042China The Institute of Brain and Intelligence Third Military Medical UniversityChongqing400042China Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing400042China State Key Laboratory of Trauma Burn and Combined InjuryDaping HospitalThird Military Medical UniversityChongqing400042China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai201200China Department of Neurology Nanchong Central HospitalThe Second Clinical Medical SchoolNorth Sichuan Medical CollegeNanchong637000China

Deficits in the clearance of amyloidβprotein(Aβ)by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer’s disease(AD).Impaired uptake of Aβby dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβclearance in AD.In the current study,flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin(PSK)on AD-related pathology in vitro and in vivo.We found that PSK,widely used in therapy for various cancers,has the potential to enhance Aβuptake and intracellular processing by human monocytes in vitro.After administration of PSK by intraperitoneal injection,APP/PS1 mice performed better in behavioral tests,along with reduced Aβdeposition,neuroinflammation,neuronal loss,and tau hyperphosphorylation.These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβclearance by blood monocytes and alleviating AD-like pathology.

关键词： Alzheimer’s disease Aβuptake Polysaccharide krestin Monocyte

Clinical Research on Alzheimer's Disease: Progress and Perspectives

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Neuroscience bulletin 2018年第6期34卷 1111-1118页

作者： Bin-Lu Sun Wei-Wei Li Chi Zhu Wang-Sheng Jin Fan Zeng Yu-Hui Liu Xian-le Bu Jie Zhu Xiu-Qing Yao Yan-Jiang Wang Department of Neurology Daping Hospital Third Military Medical University State Key Laboratory of Trauma Burn and Combined InjuryInstitute of Surgery Research Daping Hospital Third Military Medical University

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(Ab), 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.

关键词： Alzheimer's disease Amyloid-beta Tau Immunotherapy BACE1 inhibitor 5-HT6 receptor antagonist Primary prevention Positron emission tomographic imaging Biomarker

Improving Blood Monocyte Energy Metabolism Enhances Its Ability to Phagocytose Amyloid-βand Prevents Alzheimer’s Disease-Type Pathology and Cognitive Deficits

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Neuroscience bulletin 2023年第12期39卷 1775-1788页

作者： Zhi-Hao Liu Yu-Di Bai Zhong-Yuan Yu Hui-Yun Li Jie Liu Cheng-Rong Tan Gui-Hua Zeng Yun-Feng Tu Pu-Yang Sun Yu-Juan Jia Jin-Cai He Yan-Jiang Wang Xian-le Bu Department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325000China Department of Neurology and Centre for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing400042China Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing400042China Institute of Brain and Intelligence Third Military Medical UniversityChongqing400042China State Key Laboratory of Trauma Burns and Combined InjuryThird Military Medical UniversityChongqing400042China Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai201200China

Deficiencies in the clearance of peripheral amyloidβ(Aβ)play a crucial role in the progression of Alzheimer’s disease(AD).Previous studies have shown that the ability of blood monocytes to phagocytose Aβis decreased in AD.However,the exact mechanism of Aβclearance dysfunction in AD monocytes remains unclear.In the present study,we found that blood monocytes in AD mice exhibited decreases in energy metabolism,which was accompanied by cellular senescence,a senescence-associated secretory phenotype,and dysfunctional phagocytosis of Aβ.Improving energy metabolism rejuvenated monocytes and enhanced their ability to phagocytose Aβin vivo and in vitro.Moreover,enhancing blood monocyte Aβphagocytosis by improving energy metabolism alleviated brain Aβdeposition and neuroinflammation and eventually improved cognitive function in AD mice.This study reveals a new mechanism of impaired Aβphagocytosis in monocytes and provides evidence that restoring their energy metabolism may be a novel therapeutic strategy for AD.

关键词： Alzheimer's disease Aβclearance Monocyte Phagocytosis Energy metabolism

Removable urea solves the COF dilemma

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Science China Chemistry 2022年第7期65卷 1221-1222页

作者： xian-He bu School of Materials Science and Engineering Nankai UniversityTianjin 300350China

Since the first report in 2005 [1], covalent organic frameworks(COFs) have become a major platform for materials design owing to their high crystallinity, low density, large surface area, tailorable pore aperture, and versatile molecular architecture, which has attracted wide attention in gas storage, separation, electronics, and catalysis [2–5].

关键词： versatile catalysis separation

‘All-in-one’ strategy for metalla[3]catenanes and ring-in-ring complex

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National Science Review 2021年第5期8卷 14-15页

作者： xian-He bu School of Materials Science and Engineering National Institute for Advanced MaterialsNankai University

Research into mechanically interlocked molecules, such as catenanes, rotaxanes and molecular knots, has been gaining momentum in recent decades, not only because of their intriguing structures and topological importance, but also because of their important applications as molecular machines and nanoscale devices [1,2]. In addition to traditional organic macrocycles based on covalent bonds,

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Association of Polygenic Risk Score with Age at Onset and Cerebrospinal Fluid Biomarkers of Alzheimer’s Disease in a Chinese Cohort

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Neuroscience bulletin 2020年第7期36卷 696-704页

作者： Wei-Wei Li Zhen Wang Dong-Yu Fan Ying-Ying Shen Dong-Wan Chen Hui-Yun Li Ling Li Heng Yang Yu-Hui Liu Xian-le Bu Wang-Sheng Jin Fan Zeng Zhi-Qiang Xu Jin-Tai Yu Li-Yong Chen Yan-Jiang Wang Department of Neurology and Centre for Clinical Neuroscience Duping HospitalThird Military Medical UniversityChongqing 400042China Department of Anaesthesiology Daping HospitalThird Military Medical UniversityChongqing 400042China Chongqing Key Laboratory of Aging and Diseases Chongqing 400042China Centre for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghai 200031China Department of Neurology Huashan HospitalFudan UniversityShanghai 200040China

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 singlenucleotide 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.

关键词： Alzheimer's disease Single nucleotide polymorphism Polygenic risk score Cerebrospinal fluid Biomarker Amyloid-beta Tau

Preface to special issue on celebrating the 100th anniversary of Xinjiang University

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Nano Research 2024年第1期17卷 1-4页

作者： Dianzeng Jia Ruimao Hua xian-He bu Yuliang Li State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources College of ChemistryXinjiang UniversityUrumqi 830017China Department of Chemistry Tsinghua UniversityBeijing 100084China School of Materials Science and Engineering Nankai UniversityTianjin 300350China CAS Key Laboratory of Organic Solids Institute of ChemistryChinese Academy of SciencesBeijing 100190China

Xinjiang University originated from Xinjiang College of Russian Language,Political Science and Law in 1924.In 1935 and 1960,the college was re-organized and re-named as Xinjiang College and Xinjiang University,respectively.In 1978,Xinjiang University was appointed by the State Council as the only national key university in Xinjiang.In 1997,it was designated as one of the first batch of key construction universities in the“211 Project”of China.In 2000,Xinjiang University was rebuilt through merging with Xinjiang Institute of Technology.

关键词： Xinjiang anniversary originated