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Advances in longitudinal studies of amnestic mild cognitive impairment and alzheimer's disease based on multi-modal MRI techniques

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Neuroscience Bulletin 2014年第2期30卷 198-206页

作者： Zhongjie Hu Liyong Wu Jianping Jia Ying Han Department of Neurology Xuan Wu Hospital Capital Medical University Postgraduates Institute Capital Medical University alzheimer's disease center Beijing Institute for Brain Disorders

Amnestic mild cognitive impairment （aMCI） is a prodromal stage of alzheimer＇s disease （AD）, and 75%-80% of aMCI patients finally develop AD. so, early identification of patients with aMCI or AD is of great significance for prevention and intervention. According to cross-sectional studies, it is known that the hippocampus, posterior cingulate cortex, and corpus callosum are key areas in studies based on structural MRI （sMRI）, functional MRI （fMRI）, and diffusion tensor imaging （DTI） respectively. Recently, longitudinal studies using each MRI modality have demonstrated that the neuroimaging abnormalities generally involve the posterior brain regions at the very beginning and then gradually affect the anterior areas during the progression of aMCI to AD. However, it is not known whether follow-up studies based on multi-modal neuroimaging techniques （e.g., sMRI, fMRI, and DTI） can help build effective MRI models that can be directly applied to the screening and diagnosis of aMCI and AD. Thus, in the future, large-scale multi-center follow-up studies are urgently needed, not only to build an MRI diagnostic model that can be used on a single person, but also to evaluate the variability and stability of the model in the general population. In this review, we present longitudinal studies using each MRI modality separately, and then discuss the future directions in this field.

关键词： magnetic resonance imaging amnestic mild cognitive impairment alzheimer＇s disease multi-modality longitudinal studies

Patient with frontal-variant syndrome in early-onset alzheimer's disease

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General Psychiatry 2020年第2期33卷 114-117页

作者： Han Cai su Ning Wei Li Xia Li shifu Xiao Lin sun Department of Geriatric Psychiatry of the Fourth People's Hospital WuhuAnhuiChina alzheimer's disease and Related Disorders center Department of Geriatric PsychiatryShanghai Mental Health CenterShanghai Jiao Tong University School of MedicineShanghaiChina

The clinical manifestation of frontal-variant alzheimer’s disease(fvAD)is not typical,and it is difficult yet necessary to differentiate fvAD from frontal-variant frontal temporal dementia(fvFD).We describe a patient with early-onset alzheimer's disease(AD)who presented with an fvFTD-like syndrome and apolipoprotein E ε3/ε4 genotype.A brain amyloid imaging procedure,11 C-Pittsburgh compound B positron emission tomography(PET),supported the final diagnosis of AD.Our present case highlights the clinical variability that characterises early-onset AD.A multimodal approach is crucial when assessing rare forms of dementia.

关键词： alzheimer diagnosis clinical

Towards Personalized Intervention for alzheimer's disease

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Genomics, Proteomics & Bioinformatics 2016年第5期14卷 289-297页

作者： Xing Peng Peiqi Xing Xiuhui Li Ying Qian Fuhai song Zhouxian Bai Guangchun Han Hongxing Lei CAs Key Laboratory of Genome sciences and Information Beijing Institute of GenomicsChinese Academy of Sciences Cunji Medical school University of Chinese Academy of Sciences Center of Alzheimer’s Disease Beijing Institute for Brain Disorders

alzheimer＇s disease （AD） remains to be a grand challenge for the international community despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripotent cells （iPsCs）. Comprehensive information collection, better understanding of the disease mech- anisms, and diversified strategies of drug development would help with more effective intervention in the foreseeable future.

关键词： alzheimer＇s disease Demographic information Genome Peripheral biomarkers iPsC technology

Mitochondrial links between brain aging and alzheimer’s disease

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Translational Neurodegeneration 2021年第3期10卷 421-431页

作者： Heather M.Wilkins Russell H.swerdlow University of Kansas alzheimer’s disease Research center Kansas CityKSUSA Departments of Neurology University of Kansas Medical CenterKansas CityKSUSA Departments of Biochemistry and Molecular Biology Medical CenterUniversity of Kansas Medical CenterKansas CityUSA Departments of Molecular and Integrative Physiology Medical CenterUniversity of Kansas Medical CenterKansas CityKSUSA

Advancing age is a major risk factor for alzheimer’s disease(AD).This raises the question of whether AD biology mechanistically diverges from aging biology or alternatively represents exaggerated aging.Correlative and modeling studies can inform this question,but without a frm grasp of what drives aging and AD it is difcult to defnitively resolve this quandary.This review speculates over the relevance of a particular hallmark of aging,mitochondrial function,to AD,and further provides background information that is pertinent to and provides perspective on this speculation.

关键词： Aging alzheimer’s disease Mitochondria Mitochondrial DNA

Biomarkers for the diagnosis of alzheimer's disease, dementia Lewy body, frontotemporal dementia and vascular dementia

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General Psychiatry 2019年第1期32卷 5-13页

作者： Joshua Marvin Anthony Maclin Tao Wang shifu Xiao Department of Geriatric Psychiatry Shanghai Mental Health CenterShanghai Jiao Tong University School of Medicine ShanghaiChina alzheimer's disease and Related Disorders center Shanghai Jiao Tong UniversityShanghaiChina Department of Neuroscience Earlham CollegeRichmondIndianaUSA

Background Dementia is a chronic brain disorder classified by four distinct diseases that impact cognition and mental degeneration. Each subgroup exhibits similar brain deficiencies and mutations. This review will focus on four dementia subgroups: alzheimer's disease, vascular dementia, frontotemporal dementia and dementia Lewy body. Aim The aim of this systematic review is to create a concise overview of unique similarities within dementia used to locate and identify new biomarker methods in diagnosing dementia. Methods 123 300 articles published after 2010 were identified from PubMed, JsTOR, WorldCat Online Computer Library and PALNI (Private Academic Library Network of Indiana) using the following search items (in title or abstract):'Neurodegenerative diseases' OR 'Biomarkers' OR 'alzheimer's disease' OR 'Frontal Temporal Lobe Dementia' OR 'Vascular Dementia, OR 'Dementia Lewy Body' OR 'Cerebral spinal Fluid' OR 'Mental Cognitive Impairment'. 47 studies were included in the qualitative synthesis. Results Evidence suggested neuroimaging with amyloid positron emission tomography (PET) scanning and newly found PET tracers to be more effective in diagnosing alzheimer's and amnesiac mental cognitive impairment than carbon-11 Pittsburgh compound-B radioisotope tracer. Newly created methods to make PET scans more accurate and practical in clinical settings signify a major shift in diagnosing dementia and neurodegenerative diseases. Conclusion Vast improvements in neuroimaging techniques have led to newly discovered biomarkers and diagnostics. Neuroimaging with amyloid PET scanning surpasses what had been considered the dominant method of neuroimaging and MRI. Newly created methods to make PET scans more accurate and practical in clinical settings signify a major shift in diagnosing dementia pathology. Continued research and studies must be conducted to improve current findings and streamline methods to further subcategorise neurodegenerative disorders and diagnosis.

关键词： Biomarkers alzheimer's disease frontotemporal dementia

Erythrocyte sphingolipid species as biomarkers of alzheimer's disease

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Journal of Pharmaceutical Analysis 2022年第1期12卷 178-185页

作者： Jericha Mill Vihar Patel Ozioma Okonkwo Lingjun Li Thomas Raife Department of Chemistry University of Wisconsin-MadisonMadisonWI53706USA Department of Pathology and Laboratory Medicine University of Wisconsin School of Medicine and Public HealthMadisonWI53705USA Clinical science center Wisconsin Alzheimer's Disease Research CenterUniversity of Wisconsin School of Medicine and Public HealthMadisonWI53792USA school of Pharmacy University of Wisconsin-MadisonMadisonWI53705USA

Diagnosing alzheimer’s disease(AD)in the early stage is challenging.Informative biomarkers can be of great value for population-based screening.Metabolomics studies have been used to find potential biomarkers,but commonly used tissue sources can be difficult to obtain.The objective of this study was to determine the potential utility of erythrocyte metabolite profiles in screening for AD.Unlike some commonly-used sources such as cerebrospinal fluid and brain tissue,erythrocytes are plentiful and easily accessed.Moreover,erythrocytes are metabolically active,a feature that distinguishes this sample source from other bodily fluids like plasma and urine.In this preliminary pilot study,the erythrocyte metabolomes of 10 histopathologically confirmed AD patients and 10 patients without AD(control(CTRL))were compared.Whole blood was collected post-mortem and erythrocytes were analyzed using ultraperformance liquid chromatography tandem mass spectrometry.Over 750 metabolites were identified in AD and CTRL erythrocytes.seven were increased in AD while 24 were decreased(Ps increased in AD were associated with amino acid metabolism and all of the decreased metabolites were associated with lipid metabolism.Prominent among the potential biomarkers were 10 sphingolipid or sphingolipid-related species that were consistently decreased in AD patients.sphingolipids have been previously implicated in AD and other neurological conditions.Furthermore,previous studies have shown that erythrocyte sphingolipid concentrations vary widely in normal,healthy adults.Together,these observations suggest that certain erythrocyte lipid phenotypes could be markers of risk for development of AD.

关键词： alzheimer’s disease Neurodegenerative disease Mass spectrometry Erythrocytes Biomarkers Metabolomics

Multi-faceted small molecule for alzheimer’s disease

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Neural Regeneration Research 2023年第10期18卷 2198-2199页

作者： Min Hee Park Hee Kyung Jin Jae-sung Bae KNU alzheimer’s disease Research Institute Department of PhysiologySchool of MedicineKyungpook National UniversityDaeguSouth Korea KNU alzheimer’s disease Research Institute Department of Laboratory Animal MedicineCollege of Veterinary MedicineKyungpook National UniversityDaeguSouth Korea

The main pathologies of alzheimer’s disease(AD)are the accumulation of amyloid-B(AB)and tau ta ngles,and these two fundamental pathologies accompany the va rious neuropathological features,such as neuroinfla mmation,... 详细信息

关键词： alzheimer tau amyloid

Case of early-onset alzheimer’s disease with atypical manifestation

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General Psychiatry 2021年第1期34卷 49-52页

作者： Lin Zhu Limin sun Lin sun shifu Xiao Department of Rehabilitation Medicine Shanghai No.3 Rehabilitation HospitalShanghaiChina Department of Rehabilitation Medicine Huashan Hospital Fudan UniversityShanghaiChina Department of Geriatric Psychiatry Shanghai Mental Health CenterShanghaiChina alzheimer's disease and Related Disorders center Shanghai Jiao Tong UniversityShanghaiChina

short-term memory decline is the typical clinical manifestation of alzheimer’s disease(AD).However,early-onset AD usually has atypical symptoms and may get misdiagnosed.In the present case study,we reported a patient who experienced symptoms of memory loss with progressive non-fluent aphasia accompanied by gradual social withdrawal.He did not meet the diagnostic criteria of AD based on the clinical manifestation and brain MRI.However,his cerebrospinal fluid examination showed a decreased level of beta-amyloid 42,and increased total tau and phosphorylated tau.Massive amyloid β-protein deposition by 11C-Pittsburgh positron emission tomography confirmed the diagnosis of frontal variant AD.This case indicated that early-onset AD may have progressive non-fluent aphasia as the core manifestation.The combination of individual and precision diagnosis would be beneficial for similar cases.

关键词： diagnosis alzheimer tau

Myelin repair in alzheimer’s disease:a review of biological pathways and potential therapeutics

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Translational Neurodegeneration 2022年第1期11卷 219-234页

作者： Lauren Rose Hirschfeld shannon L.Risacher Kwangsik Nho Andrew J.saykin stark Neurosciences Research Institute Indiana University School of MedicineIndianapolisINUSA Indiana alzheimer’s disease Research center Indiana University School of MedicineIndianapolisINUSA Department of Radiology and Imaging sciences Indiana University School of MedicineIndianapo-lisINUSA school of Informatics and Computing Indiana University-Purdue University IndianapolisIndianapolisINUSA.

This literature review investigates the significant overlap between myelin-repair signaling pathways and pathways known to contribute to hallmark pathologies of alzheimer’s disease(AD).We discuss previously investigated therapeutic targets of amyloid,tau,and ApoE,as well as other potential therapeutic targets that have been empirically shown to contribute to both remyelination and progression of AD.Current evidence shows that there are multiple AD-relevant pathways which overlap significantly with remyelination and myelin repair through the encouragement of oligodendrocyte proliferation,maturation,and myelin production.There is a present need for a single,cohesive model of myelin homeostasis in AD.While determining a causative pathway is beyond the scope of this review,it may be possible to investigate the pathological overlap of myelin repair and AD through therapeutic approaches.

关键词： Myelin alzheimer’s disease Myelin repair Oligodendrocyte Remyelination