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Biofluid Biomarkers of Alzheimer's Disease:Progress,Problems,and Perspectives

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Neuroscience Bulletin 2022年第6期38卷 677-691页

作者： Shan Huang Yan-Jiang Wang Junhong Guo Department of Neurology First HospitalShanxi Medical UniversityTaiyuan 030000China Department of Neurology and Centre for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing 400042China

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.

关键词： Alzheimer's disease Biomarker Amyloidbeta Tau Diagnosis

Meningeal Lymphatic Vessels:A Drain of the Brain Involved in Neurodegeneration?

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Neuroscience Bulletin 2020年第5期36卷 557-560页

作者： Yuan Cheng Yan-Jiang Wang Department of Neurology and Center for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing 400042China Chongqing Key Laboratory of Aging and Brain Diseases Chongqing 400042.China The Institute of Brain and Intelligence Third Military Medical UniversityChongqing 400042China

Neurodegenerative diseases include several kinds of neurological disorder that are caused by the progressive death of neurons in different regions of the brain.Such diseases affect millions of people worldwide and impose a heavy health burden on modern societies.However,their pathogenesis remains elusive,and disease-modifying methods are not currently available to prevent,halt,or reverse them[1].

关键词： degeneration diseases death

Early Intervention in Alzheimer’s Disease: How Early is Early Enough?

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Neuroscience Bulletin 2020年第2期36卷 195-197页

作者： Dong-Yu Fan Yan-Jiang Wang Department of Neurology and Center for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing 400042China Chongqing Key Laboratory of Aging and Brain Diseases Chongqing 400042China

In 1906,Dr.Alois Alzheimer reported a case of dementia and thought it was a new type of disease.Later,Dr.Emil Kraepelin named it Alzheimer’s disease(AD).One hundred years later,AD has become the most common type of dementia affecting the elderly population and a heavy health burden.However,the pathogenesis of the disease remains unclear,and no disease-modifying therapies are available to prevent,halt,or even slow the progression of the disease[1].

关键词： Alzheimer pathogenesis Early

Combining Multiple Factors to Predict Alzheimer’s Disease

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Neuroscience Bulletin 2022年第8期38卷 969-972页

作者： Xiao-Lin Gao Jun wang Yan-Jiang Wang Xian-Le Bu Department of Neurology and Centre for Clinical Neuroscience Daping HospitalThird Military Medical University400042ChongqingChina Chongqing Key Laboratory of Ageing and Brain Diseases 400042ChongqingChina Institute of Brain and Intelligence Third Military Medical University400042ChongqingChina State Key Laboratory of Trauma Burns and Combined InjuryThird Military Medical University400042ChongqingChina Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of Sciences200031ShanghaiChina

Alzheimer's disease(AD)is the most common type of dementia that imposes a high burden on caregivers and has substantial economic cost for society.Although there are no drugs available to reverse the progression of AD,a large number of studies have shown that intervention for the risk factors for AD or administration of disease-modifying therapy at the preclinical/prodromal stage yields better outcomes.Therefore,early diagnosis or accurate prediction of AD in healthy populations and preclinical AD is an important prerequisite for effective intervention.

关键词： Alzheimer diagnosis drugs

White Matter“Matters”in Alzheimer’s Disease

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Neuroscience Bulletin 2022年第3期38卷 323-326页

作者： Man-Yu Xu Zhi-Qiang Xu Yan-Jiang Wang Department of Neurology and Center for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqing400042China Chongqing Key Laboratory of Ageing and Brain Diseases Chongqing400042China The Institute of Brain and Intelligence Third Military Medical UniversityChongqing400042China

Alzheimer's disease(AD)is a neurodegenerative disease that increasingly burdens many families worldwide.Although AD is generally thought to be closely associated with gray matter,many studies have identified significant changes in white matter as well,including demyelination and function alterations in oligodendrocytes in the AD brain.In addition,Ap plaques,the most important pathological characteristic in AD,are deposited in late-myelinating regions such as the prefrontal and temporal lobes,where myelin is prone to damage[1].All the evidence hints that the changes in myelin are closely associated with the onset and progression of AD,prompting scientists to outline the process of changing myelin in AD and develop novel strategies for the treatment of AD.

关键词： Alzheimer alterations damage

A θ-L APPROACH FOR SOLVING SOLID-STATE DEWETTING PROBLEMS

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Journal of Computational Mathematics 2022年第2期40卷 275-293页

作者： Weijie Huang Wei jiang yan wang Beijing Computational Science Research Center Beijing 100193China School of Mathematics and Statistics Wuhan UniversityWuhan 430072China Hubei Key Laboratory of Computational Science Wuhan UniversityWuhan 430072China School of Mathematics and Statistics Central China Normal UniversityWuhan 430079China

We propose a θ-L approach for solving a sharp-interface model about simulating solid-state dewetting of thin films with isotropic/weakly anisotropic surface energies.The sharp-interface model is governed by surface diffusion and contact line migration.For solving the model,traditional numerical methods usually suffer from the severe stability constraint and/or the mesh distribution trouble.In the θ-L approach,we introduce a useful tangential velocity along the evolving interface and utilize a new set of variables(i.e.,the tangential angle 6 and the total length L of the interface curve),so that it not only could reduce the stiffness resulted from the surface tension,but also could ensure the mesh equidistri-bution property during the evolution.Furthermore,it can achieve second-order accuracy when implemented by a semi-implicit linear finite element method.Numerical results are reported to demonstrate that the proposed θ-L approach is efficient and accurate.

关键词： Solid-state dewetting,Surface diffusion Moving contact lines Anisotropic surface energy θ-L formulation Finite element method

Peripheral clearance of brain-derived Aβ in Alzheimer's disease: pathophysiology and therapeutic perspectives

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Translational Neurodegeneration 2020年第2期9卷 178-188页

作者： Yuan Cheng Ding-Yuan Tian Yan-Jiang Wang Department of Neurology and Centre for Clinical Neuroscience Daping HospitalThird Military Medical UniversityChongqingChina The Institute of Brain and Intelligence Third Military Medical UniversityChongqingChina Key Laboratory of Aging and Brain Diseases ChongqingChina Center for Excellence in Brain Science and Intelligence Technology Chinese Academy of SciencesShanghaiChina

Alzheimer’s disease(AD)is the most common type of dementia,and no disease-modifying treatments are available to halt or slow its progression.Amyloid-beta(Aβ)is suggested to play a pivotal role in the pathogenesis of AD,and clearance of Aβfrom the brain becomes a main therapeutic strategy for AD.Recent studies found that Aβclearance in the periphery contributes substantially to reducing Aβaccumulation in the brain.Therefore,understanding the mechanism of how Aβis cleared in the periphery is important for the development of effective therapies for AD.In this review,we summarized recent findings on the mechanisms of Aβefflux from the brain to the periphery and discuss where and how the brain-derived Aβis cleared in the periphery.Based on these findings,we propose future strategies to enhance peripheral Aβclearance for the prevention and treatment of AD.This review provides a novel perspective to understand the pathogenesis of AD and develop interventions for this disease from a systemic approach.

关键词： Alzheimer's disease Beta-amyloid Blood-brain barrier Lymphatic vessel Venous sinus Periphery Liver Kidney Intestine Skin Blood Monocyte Enzymes

Fully distributed identity-based threshold signatures with identifiable aborts

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Frontiers of Computer Science 2023年第5期17卷 179-195页

作者： yan jiang Youwen ZHU Jian wang Xingxin LI College of Computer Science and Technology Nanjing University of Aeronautics and AstronauticsNanjing 211106China State Key Laboratory of Integrated Services Networks(Xidian University) Xi’an 710071China Guangxi Key Laboratory of Trusted Software Guilin University of Electronic TechnologyGuilin 541004China Department of Mathematical Informatics University of TokyoTokyo 113-8654Japan

Identity-based threshold signature(IDTS)is a forceful primitive to protect identity and data privacy,in which parties can collaboratively sign a given message as a signer without reconstructing a signing key.Nevertheless,most IDTS schemes rely on a trusted key generation center(KGC).Recently,some IDTS schemes can achieve escrow-free security against corrupted KGC,but all of them are vulnerable to denial-of-service attacks in the dishonest majority setting,where cheaters may force the protocol to abort without providing any feedback.In this work,we present a fully decentralized IDTS scheme to resist corrupted KGC and denialof-service attacks.To this end,we design threshold protocols to achieve distributed key generation,private key extraction,and signing generation which can withstand the collusion between KGCs and signers,and then we propose an identification mechanism that can detect the identity of cheaters during key generation,private key extraction and signing generation.Finally,we formally prove that the proposed scheme is threshold unforgeability against chosen message attacks.The experimental results show that the computation time of both key generation and signing generation is<1 s,and private key extraction is about 3 s,which is practical in the distributed environment.

关键词： threshold signatures single points of failure identifiable aborts

Euphoric effect induced by zolpidem:a case study of magnetoencephalography

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General Psychiatry 2022年第1期35卷 61-66页

作者： Xuechan Lyu Yegang Hu yan Zhao Haihong wang jiang Du Jijun wang Haifeng jiang Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineShanghaiChina Shanghai Key Laboratory of Psychotic Disorders ShanghaiChina

Initially,zolpidem,a non-benzodiazepine hypnotic agent,was considered to have fewer adverse reactions than traditional benzodiazepines.However,after zolpidem was approved for medical use,an increasing number of case reports have described abuse or dependence complications.We were especially interested in the cases of dependence that presented a paradoxical‘euphoric’effect of zolpidem.This article reports the case of a female zolpidem-dependent patient who presented with 6 years of daily use of 400-1400 mg of zolpidem.She reported subjective effects of euphoria,intense craving and the inability to stop drug ingestion.Her diagnoses were zolpidem dependence and a depressive episode induced by substance abuse.To explore the neural mechanisms of the euphoric effect caused by high-dose zolpidem,we performed repeated magnetoencephalography(MEG)recordings.Before undergoing detoxification,her MEG results indicated that cerebellar electrical signal activation increased when taking high zolpidem doses.However,the prefrontal and parietal lobes’electrical signal activity showed a tendency to recover to a normal state as the withdrawal time progressed to completion.This case suggests that the cerebellum plays a role in the euphoria induced by high zolpidem doses and provides clues for further research.

关键词： effect magneto intense