Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the...Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.展开更多
Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,ta...Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.展开更多
目的观察^(18)F-flortaucipir tau PET联合APOEε4基因携带状态对轻度认知障碍(MCI)的诊断价值。方法于阿尔茨海默病神经成像倡议(ADNI)数据集中选取213例MCI(MCI组)及402名健康对照(HC组),对比分析其神经心理学信息、APOEε4基因携带...目的观察^(18)F-flortaucipir tau PET联合APOEε4基因携带状态对轻度认知障碍(MCI)的诊断价值。方法于阿尔茨海默病神经成像倡议(ADNI)数据集中选取213例MCI(MCI组)及402名健康对照(HC组),对比分析其神经心理学信息、APOEε4基因携带状态、tau PET及高分辨结构MRI数据;利用随机森林法筛选tau PET诊断MCI的重要脑区,比较tau PET鉴别携带/未携带APOEε4基因MCI与HC的效能。结果利用tau PET诊断MCI的重要脑区依次为杏仁核、海马旁回、内嗅皮层、后扣带回、颞下回、梭状回及颞中回。基于上述7个脑区ROI构建的tau PET标准摄取值比值(SUVR)模型鉴别携带APOEε4基因MCI与HC的准确率及曲线下面积(AUC)分别为86.68%及0.784,高于其鉴别MCI与HC、未携带APOEε4基因MCI与HC(准确率分别为70.57%及75.05%,AUC分别为0.711及0.609)。结论基于杏仁核、海马旁回、内嗅皮层、后扣带回、颞下回、梭状回及颞中回构建的^(18)F-flortaucipir tau PET SUVR模型可用于诊断MCI;联合APOEε4基因可进一步提高其诊断效能。展开更多
基金supported by the Nature Science Foundation of Liaoning Province,Nos.2022-MS-211,2021-MS-064,and 2024-MS-048(all to YC).
文摘Alzheimer’s disease,a devastating neurodegenerative disorder,is characterized by progressive cognitive decline,primarily due to amyloid-beta protein deposition and tau protein phosphorylation.Effectively reducing the cytotoxicity of amyloid-beta42 aggregates and tau oligomers may help slow the progression of Alzheimer’s disease.Conventional drugs,such as donepezil,can only alleviate symptoms and are not able to prevent the underlying pathological processes or cognitive decline.Currently,active and passive immunotherapies targeting amyloid-beta and tau have shown some efficacy in mice with asymptomatic Alzheimer’s disease and other transgenic animal models,attracting considerable attention.However,the clinical application of these immunotherapies demonstrated only limited efficacy before the discovery of lecanemab and donanemab.This review first discusses the advancements in the pathogenesis of Alzheimer’s disease and active and passive immunotherapies targeting amyloid-beta and tau proteins.Furthermore,it reviews the advantages and disadvantages of various immunotherapies and considers their future prospects.Although some antibodies have shown promise in patients with mild Alzheimer’s disease,substantial clinical data are still lacking to validate their effectiveness in individuals with moderate Alzheimer’s disease.
文摘Tau plays a crucial role in several neurodegenerative diseases,collectively referred to as tauopathies.Therefore,targeting potential pathological changes in tau could enable useful therapeutic interventions.However,tau is not an easy target because it dynamically interacts with microtubules and other cellular components,which presents a challenge for tau-targeted drugs.New cellular models could aid the development of mechanism-based tau-targeted therapies.
文摘目的观察^(18)F-flortaucipir tau PET联合APOEε4基因携带状态对轻度认知障碍(MCI)的诊断价值。方法于阿尔茨海默病神经成像倡议(ADNI)数据集中选取213例MCI(MCI组)及402名健康对照(HC组),对比分析其神经心理学信息、APOEε4基因携带状态、tau PET及高分辨结构MRI数据;利用随机森林法筛选tau PET诊断MCI的重要脑区,比较tau PET鉴别携带/未携带APOEε4基因MCI与HC的效能。结果利用tau PET诊断MCI的重要脑区依次为杏仁核、海马旁回、内嗅皮层、后扣带回、颞下回、梭状回及颞中回。基于上述7个脑区ROI构建的tau PET标准摄取值比值(SUVR)模型鉴别携带APOEε4基因MCI与HC的准确率及曲线下面积(AUC)分别为86.68%及0.784,高于其鉴别MCI与HC、未携带APOEε4基因MCI与HC(准确率分别为70.57%及75.05%,AUC分别为0.711及0.609)。结论基于杏仁核、海马旁回、内嗅皮层、后扣带回、颞下回、梭状回及颞中回构建的^(18)F-flortaucipir tau PET SUVR模型可用于诊断MCI;联合APOEε4基因可进一步提高其诊断效能。
