Alzheimer

摘要： Potential causes for the clinical and pathological variability observed in Alzheimer’s disease(AD):AD is an age-related neurodegenerative disorder characterized by the impairment of cognitive functions such as memory,learning,and reasoning.These commonly described clinical symptoms are due to particular pathological changes in the brain,including inflammation,synaptic loss,and neuronal death.These changes are a consequence of the accumulation of abnormally folded amyloid-β(Aβ)and tau proteins in specific areas of the central nervous system.Considering the progressive aging of the world’s population,the number of people affected by AD is expected to substantially and consistently increase in the coming years.This positions AD as one of the main public health challenges in the near future.

摘要： The amyloid cascade hypothesis of Alzheimer’s pathogenesis:The amyloid cascade hypothesis of Alzheimer’s disease(AD)pathogenesis will shortly celebrate its thirtieth birthday(Hardy and Higgins,1992).Based on abundant genetic and biochemical evidence,it proposes that deposition of the amyloid-β(Aβ)peptide in brain parenchyma is an essential upstream trigger in AD pathogenesis that drives a cascade of events,specifically including the recruitment and pathological hyper-phosphorylation of the micro-tubule-associated protein tau,that culminate in derangement of synaptic function and,eventually,neuronal death.

摘要： Dementia,for which there is no cure or effective treatment,is the leading cause of disability and death worldwide.Due to the high global prevalence and economic impact on families,caregivers,and communities,this condition represents one of the most significant public health challenges of our time.Dementia is an umbrella term describing a range of progressive neurodegenerative diseases,including Alzheimer’s disease(AD),which is the most common cause of cognitive and functional impairment among older adults.The presence of misfolded protein aggregates characterizes neurodegenerative disorders(e.g.,amyloid-beta(Aβ)and tau in AD).

摘要： Tau is an important protein of the central nervous system formed by 352-441 amino acids and encoded by the MAPT(microtubule-associated protein tau)gene on chromosome 17 which generates 6 isoforms.Tau is located in axons,dendrites,nucleus,cell membrane,and synapses of neurons.The protein is also expressed to a lesser extent in astrocytes and oligodendrocytes,although its role in these cells has been little investigated.The protein is also present in the interstitial fluid and can cross into the cerebrospinal fluid(CSF)and reach the systemic circulation.

摘要： Lipids play essential biological functions that include acting as components of biological membranes,energy storage,signaling,nutrients,transporters,enzyme activators,among others.Compared with the multiple research methods to assess DNA,RNA,and protein content,location,and function in cells,there are relatively fewer methods to study lipids.Therefore,lipid-oriented mechanistic studies remain rare and challenging.

摘要： Biological models of Alzheimer’s disease(AD):Non-human models have contributed tremendously to the understanding of AD and its underlying pathological processes.These models have aided the investigation of the genetic and environmental risk factors.They also have enabled the progression of candidate therapies into human clinical trials.Because of similarities with human brain anatomy and genetics,rodent models have been used extensively to recapitulate some aspects of AD pathology,measure AD-associated behavioral parameters and related nervous system dysfunctions(Eriksen and Janus,2007).For instance,transgenic mice overexpressing human amyloid precursor protein have furthered the development of the amyloid cascade hypothesis as a central pillar of familial AD.

摘要： Importance of TAU protein for dementia syndromes:Dementia currently affects about 55 million people worldwide,with Alzheimer's disease(AD)being the most prevalent form.The one crucial pathological hallmark of AD that correlates best with loss of synapses and cognitive decline are the so-called intracellular neurofibrillary tangles composed of mislocalized/missorted and hyperphosphorylated TAU protein(Naseri et al.,2019).Many other neurodegenerative diseases,both genetic and nongenetic,are characterized by neurofibrillary ta ngles or pathological accumulation of the protein TAU and are thus termed"tauopathies".

摘要： Alzheimer’s disease(AD)is the main neurodegenerative disease leading to dementia and cognitive impairment in the elderly.Considering AD to be an epidemic,an increase from the current 50 million to more than 150 million patients is expected by the year 2050.

摘要： The increase in the prevalence of individuals with Alzheimer's disease(AD)combined with the lack of a cure calls for the development of novel therapies against AD(Canter et al.,2016).The key disease-defining pathological features of AD are the accumulation of extracellular amyloid-beta(Aβ)plaques(accompanied by increasing intracellular Aβ_(1-42))and higher intracellular neu rofi brilla ry tangles,comprised mostly of hyperphosphorylated tau protein/pTau(Goedert,2015;Hardy,2017).It is evident that the elderly are more predisposed to develop AD,and thus aging is considered to be the primary risk factor for AD.By extra polation,strategies that delay aging may also slow down(if not stop)AD.

摘要： Alzheimer's disease is the most prevalent type of dementia today,discovered and described by Alois Alzheimer in 1907.According to the World Alzheimer Report 2021,75%of people with dementia worldwide are undiagnosed,equivalent to 41 million people(Gauthier et al.,2021).With each passing year,the number of people affected by these diseases is increasing,and the estimates of suffering from them in the future are growing.

摘要： Lack of an association between Alzheimer's disease and the cystatin C (CST3) gene G73A polymorphism in Mainland Chinese. Dement Geriatr Cogn Disord. 2008;25(5):461-4. Alzheimer's disease (AD) is a complex multifactorial disorder involving a number of genetic and environmental factors. Cystatin C (CST3)，which belongs to the type II cystatin gene family，is a potent inhibitor of lysosomal proteinaseso Immunohistochemical studies have demonstrated the colocalization of the β-amyloid (A-beta) and cystatin C peptides within arteriolar walls in the AD brain. The G73A polymorphism of the CST3 genemay be associated with AD development. To investigate a possible association between the CST3 G73A polymorphism and late-onset AD (LOAD) in Mainland Chinese，we examined 281 LOAD patients and 376 healthy controls. All subjects were genotyped for CST3 and apolipoprotein E (APOE). There were no significant differences in the CST3 genotype or allele frequencies between the cases and the controls. Likewise，with the stratification of the APOE epsilon4 status，no statistical difference was observed between the cases and the controls. Our findings suggest that this polymorphism may not represent an additional genetic risk factor for LOAD in Mainland Chinese.

摘要： Lack of an association between Alzheimer's disease and the cystatin C (CST3) gene G73A polymorphism in Mainland Chinese. Dement Geriatr Cogn Disord. 2008;25(5):461-4. Alzheimer's disease (AD) is a complex multifactorial disorder involving a number of genetic and environmental factors. Cystatin C (CST3)，which belongs to the type II cystatin gene family，is a potent inhibitor of lysosomal proteinaseso Immunohistochemical studies have demonstrated the colocalization of the β-amyloid (A-beta) and cystatin C peptides within arteriolar walls in the AD brain. The G73A polymorphism of the CST3 genemay be associated with AD development. To investigate a possible association between the CST3 G73A polymorphism and late-onset AD (LOAD) in Mainland Chinese，we examined 281 LOAD patients and 376 healthy controls. All subjects were genotyped for CST3 and apolipoprotein E (APOE). There were no significant differences in the CST3 genotype or allele frequencies between the cases and the controls. Likewise，with the stratification of the APOE epsilon4 status，no statistical difference was observed between the cases and the controls. Our findings suggest that this polymorphism may not represent an additional genetic risk factor for LOAD in Mainland Chinese.

摘要： Lack of an association between Alzheimer's disease and the cystatin C (CST3) gene G73A polymorphism in Mainland Chinese. Dement Geriatr Cogn Disord. 2008;25(5):461-4. Alzheimer's disease (AD) is a complex multifactorial disorder involving a number of genetic and environmental factors. Cystatin C (CST3)，which belongs to the type II cystatin gene family，is a potent inhibitor of lysosomal proteinaseso Immunohistochemical studies have demonstrated the colocalization of the β-amyloid (A-beta) and cystatin C peptides within arteriolar walls in the AD brain. The G73A polymorphism of the CST3 genemay be associated with AD development. To investigate a possible association between the CST3 G73A polymorphism and late-onset AD (LOAD) in Mainland Chinese，we examined 281 LOAD patients and 376 healthy controls. All subjects were genotyped for CST3 and apolipoprotein E (APOE). There were no significant differences in the CST3 genotype or allele frequencies between the cases and the controls. Likewise，with the stratification of the APOE epsilon4 status，no statistical difference was observed between the cases and the controls. Our findings suggest that this polymorphism may not represent an additional genetic risk factor for LOAD in Mainland Chinese.

摘要： 本发明涉及人巨细胞病毒潜伏感染致Alzheimer′s病模型鼠及建立方法，用于研究人类AD病的病因、病理及发病机制，其关键技术之处主要在于用HCMV AD169株感染8周龄Balb/c SPF级雌雄小鼠，建立子代小鼠Alzheimer’s病模型，此模型能全面的再现AD的行为学异常、神经病理学特征和神经生化的改变，为研究人类Alzheimer’s病的病因、病理发病机制、预防和治疗提供了工具。

摘要： 本发明公开了铂(II)配合物及其药物组合物治疗Alzheimer症的医药用途。所述铂(II)配合物为含有三齿配体和黄嘌呤衍生物配体的铂(II)配合物1和2。铂(II)配合物能够降低β‑淀粉样蛋白(Aβ)的前体蛋白APP的表达和抑制Aβ的聚集，具有抑制肿瘤干细胞、诱导肿瘤细胞发生神经细胞分化和抑制血管增生的多重抗肿瘤或治疗肿瘤的作用。

摘要： 本发明涉及人巨细胞病毒潜伏感染致Alzheimer’s病模型鼠及建立方法，用于研究人类AD病的病因、病理及发病机制，其关键技术之处主要在于用HCMV AD169株感染8周龄Balb/c SPF级雌雄小鼠，建立子代小鼠Alzheimer’s病模型，此模型能全面的再现AD的行为学异常、神经病理学特征和神经生化的改变，为研究人类Alzheimer’s病的病因、病理发病机制、预防和治疗提供了工具。

摘要： 本发明涉及一种预防和/或治疗Alzheimer症和其他与淀粉样蛋白有关的疾病的基于立体化学的“非自身”抗原疫苗。本发明提供用来预防和治疗Alzheimer症和其他与淀粉样蛋白有关的疾病的疫苗，所述疫苗克服了与使用天然产生肽，蛋白质或免疫原有关的缺点。