Alzheimer's Disease - The 21st Century Challenge最新文献

Mild Cognitive Impairment 轻度认知障碍

Alzheimer's Disease - The 21st Century Challenge Pub Date : 2018-07-18 DOI: 10.5772/INTECHOPEN.75509

M. Janelidze, N. Botchorishvili

引用次数: 3

Alzheimer’s Disease: Beyond the Neuron 阿尔茨海默病:超越神经元

Alzheimer's Disease - The 21st Century Challenge Pub Date : 2018-07-18 DOI: 10.5772/INTECHOPEN.75510

A. Verma, M. Zabel

引用次数: 0

Passive Immunotherapy in Alzheimer’s Disease 阿尔茨海默病的被动免疫治疗

Alzheimer's Disease - The 21st Century Challenge Pub Date : 2018-07-18 DOI: 10.5772/INTECHOPEN.76299

P. Dolan, W. Zago

{"title":"Passive Immunotherapy in Alzheimer’s Disease","authors":"P. Dolan, W. Zago","doi":"10.5772/INTECHOPEN.76299","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.76299","url":null,"abstract":"The development of therapeutics for the treatment of Alzheimer’s disease (AD) has been challenged with a myriad of obstacles: an evolving and incomplete understanding of disease etiology and progression, challenges with early diagnosis, multifactorial genetic and environmental factors that contribute to patient variability, and the cost of conducting lengthy clinical trials. One approach that has garnered a significant amount of attention and resources for its potential as a disease modifying approach is passive immunotherapy directed at clearing amyloid-β (Aβ) species, a pathological hallmark of Alzheimer’s disease. While passive immunotherapeutic trials directed at Aβ have not yet demonstrated clinical benefit, they have prompted important advances in the application and understanding of biomarkers, patient selection, novel functional readouts, and safety monitoring. Application of these lessons has enabled more recent clinical trials to incorporate better trial designs and refine inclusion criteria to optimize patient population enrollment. In addition, new passive immunotherapy targets emerging in the clinic have emerged, as well as novel technologies to enhance future antibody therapeutics. Taken together, the advances in research and clinical science have prepared the passive immunotherapy field to advance emerging promising disease modifying treatments in AD.","PeriodicalId":437558,"journal":{"name":"Alzheimer's Disease - The 21st Century Challenge","volume":"425 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126717340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Lithium and Alzheimer’s Disease: Experimental, Epidemiological, and Clinical Findings 锂与阿尔茨海默病:实验、流行病学和临床发现

Alzheimer's Disease - The 21st Century Challenge Pub Date : 2018-07-18 DOI: 10.5772/intechopen.74239

J. Rybakowski

{"title":"Lithium and Alzheimer’s Disease: Experimental, Epidemiological, and Clinical Findings","authors":"J. Rybakowski","doi":"10.5772/intechopen.74239","DOIUrl":"https://doi.org/10.5772/intechopen.74239","url":null,"abstract":"Alzheimer’s disease (AD) represents one of the greatest health-care challenges of the twenty-first century. Besides known pathologies such as intracellular accumulation of neurofibrillary tangles and extracellular deposition of amyloid-beta plaques, other factors, such as dysregulated GSK-3 activity, mitochondrial dysfunction, inflammation, and oxidative stress, have been shown to play a role in the pathogenesis of AD. Over the last two decades, the evidence accumulated for a neuroprotective effect of lithium, as an important mechanism of this ion in mood disorders, reflected by an increase in cerebral gray matter volume in lithium-treated subjects. Neurobiological mechanisms of lithium neuroprotective actions may also be relevant to the pathogenesis and treatment of AD, and they will be delineated. In most epidemiological studies, a negative association between lithium use and dementia has been shown, including two most recent papers regarding a concentration of lithium in drinking water. In this article, the results of initial studies using lithium in the treatment of dementia and showing some promise will also be presented. Therefore, considering the current paucity of treatments for the AD, further testing of lithium as a disease-modifying treatment in this illness may be warranted.","PeriodicalId":437558,"journal":{"name":"Alzheimer's Disease - The 21st Century Challenge","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125146160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Defining Microglial Phenotypes in Alzheimer’s Disease 确定阿尔茨海默病中的小胶质细胞表型

Alzheimer's Disease - The 21st Century Challenge Pub Date : 2018-07-18 DOI: 10.5772/INTECHOPEN.75511

D. Walker, L. Lue

{"title":"Defining Microglial Phenotypes in Alzheimer’s Disease","authors":"D. Walker, L. Lue","doi":"10.5772/INTECHOPEN.75511","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75511","url":null,"abstract":"The concept of activated microglia being associated with neurodegenerative pathological structures in aging and Alzheimer’s disease (AD) has been well established, but questions remain about how well are we defining “what are microglia actually doing” when we look at diseased or aged brains? Most studies of microglia in human AD brains have employed a limited set of antigenic markers, particularly the major histocompatibility complex protein HLA-DR and ionized calcium-binding adaptor molecule IBA-1, along with cellular morphological criteria, but in recent years, it has been appreciated that microglial responses are very heterogeneous depending on their surrounding environment—every microglia might be different. Initial observations on human brain microglia associated with plaques and tangles suggested that microglial inhibition with broad spectrum anti-inflammatory drugs should slow down AD pathology, but clinical trials did not show this approach to be effective. In this article, we will consider the needs, challenges and benefits for refining how microglia are defined as they associate with pathological proteins. This may aid in defining which ones are accelerating neurotoxicity and which ones are performing reparative/phagocytic functions. More complete definition of microglial phenotypes offers the potential of developing targeted anti-inflammatory approaches for this disease.","PeriodicalId":437558,"journal":{"name":"Alzheimer's Disease - The 21st Century Challenge","volume":"75 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"131709888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial Link Between Metabolic Syndrome and Pre-Alzheimer’s Disease 代谢综合征与阿尔茨海默病前期之间的线粒体联系

Alzheimer's Disease - The 21st Century Challenge Pub Date : 2018-03-23 DOI: 10.5772/INTECHOPEN.75306

N. Apaijai, Wasana Pratchayasakul, N. Chattipakorn, S. Chattipakorn

引用次数: 1

Amyloid Beta Hypothesis: Attention to β- and γ-Secretase Modulators β淀粉样蛋白假说:关注β和γ分泌酶调节剂

Alzheimer's Disease - The 21st Century Challenge Pub Date : 2018-03-14 DOI: 10.5772/INTECHOPEN.75629

J. Korábečný, K. Spilovska, O. Soukup, R. Doležal, K. Kuča

{"title":"Amyloid Beta Hypothesis: Attention to β- and γ-Secretase Modulators","authors":"J. Korábečný, K. Spilovska, O. Soukup, R. Doležal, K. Kuča","doi":"10.5772/INTECHOPEN.75629","DOIUrl":"https://doi.org/10.5772/INTECHOPEN.75629","url":null,"abstract":"The amyloid cascade hypothesis poses one possible explanation for the onset and progres- sion of Alzheimer’s disease (AD). With this respect, neurotoxic effect is attributed to soluble and diffusive amyloid-β (Aβ) oligomers. Aβ peptides are produced by proteolytic cleavage of the hydrophobic transmembrane portion of the amyloid precursor protein (APP) by suc-cessive action of β- and γ-secretases. Aβ peptides are generated in several isoforms, out of which the most pronounced are Aβ40 and Aβ42 being the major constituents of amyloid plaques found in AD patients’ brains. Since the indisputable evidence pointed out to Aβ oligomers as toxic agents, several pathways to modulate or control the aggregation have been inspected . Given all these aspects, inhibitors of the β- and γ-secretases have gained the most attention. This chapter presents amyloid cascade hypothesis with current progress in the development of β- and γ-secretase modulators to counteract the Aβ burden. BACE-2 knockout (−/−) mice showed the same phenotype. Double-knockout mice, that is, mice with deactivated genes for BACE-1 (−/−) as well as for BACE-2 (−/−), are not phenotypically very different from mice without the gene for the BACE-1, with the exception of an increased num ber of dying mice freshly after birth. The results of this study therefore assume that nonselective inhibitors of both subtypes of the enzyme BACE may be well tolerated at least from the perspec tive of the inhibition of BACE-2. The latest research has shown that BACE-2 is expressed in the pancreatic β cells and BACE-2 knockout mice exhibit an improved glycemic regulation due to the increased production of insulin. These findings imply the possible use of BACE-2 inhibitors for the treatment of diabetes mellitus of type 2 [ 15].","PeriodicalId":437558,"journal":{"name":"Alzheimer's Disease - The 21st Century Challenge","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2018-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130865034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Challenges in Dementia Studies 痴呆症研究面临的挑战

Alzheimer's Disease - The 21st Century Challenge Pub Date : 2017-12-20 DOI: 10.5772/INTECHOPEN.72866

Kevin T Ong

引用次数: 0