Alzheimer's disease.

文献信息

DOI	10.1016/S0140-6736(20)32205-4
PMID	33667416
期刊	Lancet (London, England)
发表年份	2021
被引次数	1897
关键词	阿尔茨海默病, 生物标志物, 遗传风险, 生活方式干预, 药物治疗
文献类型	Journal Article, Review
ISSN	0140-6736
页码	1577-1590
期号	397(10284)
作者	Philip Scheltens, Bart De Strooper, Miia Kivipelto, Henne Holstege, Gael Chételat, Charlotte E Teunissen, Jeffrey Cummings, Wiesje M van der Flier

一句话小结

本研究探讨了阿尔茨海默病的最新进展，指出到2050年欧洲和全球的痴呆症患病率将显著增加，且遗传因素对风险的贡献高达60-80%。此外，研究还强调了新型生物标志物的潜力及生活方式干预对认知功能的积极影响，显示出在临床和预防方面的重大意义。

在麦伴科研 (maltsci.com) 搜索更多文献

阿尔茨海默病 · 生物标志物 · 遗传风险 · 生活方式干预 · 药物治疗

摘要

在本次研讨会上，我们强调阿尔茨海默病领域的主要进展。最新数据显示，到2050年，欧洲的痴呆症患病率将翻倍，全球则将增加三倍；而基于生物学（而非临床）定义的阿尔茨海默病，这一估计的增幅更是达到三倍。阿尔茨海默病的最早阶段（细胞阶段）与淀粉样β的积累并行发生，导致tau病理的传播。阿尔茨海默病的风险有60-80%依赖于遗传因素，目前已经识别出40多个与阿尔茨海默病相关的遗传风险位点，其中APOE等位基因与该疾病的关联最为显著。新型生物标志物包括用于淀粉样β和磷酸化tau的PET扫描和血浆检测，这在临床和研究中展现出巨大的潜力。基于多领域生活方式的预防试验表明，在痴呆症风险增加的参与者中可获得认知益处。生活方式因素并不会直接影响阿尔茨海默病的病理，但仍可对阿尔茨海默病患者的积极结果产生贡献。有前景的药物治疗正处于临床试验的高级阶段，包括抗淀粉样β、抗tau和抗炎策略。

英文摘要

In this Seminar, we highlight the main developments in the field of Alzheimer's disease. The most recent data indicate that, by 2050, the prevalence of dementia will double in Europe and triple worldwide, and that estimate is 3 times higher when based on a biological (rather than clinical) definition of Alzheimer's disease. The earliest phase of Alzheimer's disease (cellular phase) happens in parallel with accumulating amyloid β, inducing the spread of tau pathology. The risk of Alzheimer's disease is 60-80% dependent on heritable factors, with more than 40 Alzheimer's disease-associated genetic risk loci already identified, of which the APOE alleles have the strongest association with the disease. Novel biomarkers include PET scans and plasma assays for amyloid β and phosphorylated tau, which show great promise for clinical and research use. Multidomain lifestyle-based prevention trials suggest cognitive benefits in participants with increased risk of dementia. Lifestyle factors do not directly affect Alzheimer's disease pathology, but can still contribute to a positive outcome in individuals with Alzheimer's disease. Promising pharmacological treatments are poised at advanced stages of clinical trials and include anti-amyloid β, anti-tau, and anti-inflammatory strategies.

麦伴智能科研服务

智能阅读回答你对文献的任何问题，帮助理解文献中的复杂图表和公式

定位观点定位某个观点在文献中的蛛丝马迹

加入知识库完成数据提取，报告撰写等更多高级知识挖掘功能

主要研究问题

核心洞察

研究背景和目的

阿尔茨海默病（AD）是导致痴呆的主要原因，预计到2050年，全球痴呆症的患病率将增加三倍。研究的目的是提供对阿尔茨海默病领域最新进展的全面了解，包括病理机制、遗传风险因素、成像生物标志物以及生活方式干预的效果。

主要方法/材料/实验设计

本研究采用文献回顾的方式，分析了2010年至2020年间的相关研究。重点关注生物标志物的进展和生活方式干预的影响。以下是技术路线的流程图：

关键结果和发现

病理机制：阿尔茨海默病的早期阶段与淀粉样β的积累和tau蛋白病理的扩散相关。
遗传因素：60-80%的风险与遗传因素有关，已识别出超过40个与阿尔茨海默病相关的遗传风险位点，APOE ε4等位基因与疾病关联最强。
生物标志物：PET扫描和血浆检测淀粉样β和磷酸化tau的生物标志物显示出良好的临床和研究应用前景。
生活方式干预：多领域的生活方式干预试验表明，对于有痴呆风险的参与者，认知能力有所改善。

主要结论/意义/创新性

研究强调了阿尔茨海默病的复杂性，指出生物标志物的使用使得在临床症状出现之前就可以进行早期诊断。此外，生活方式的干预虽然不能直接影响阿尔茨海默病的病理，但能够改善有该病风险个体的认知结果。药物治疗方面，抗淀粉样β、抗tau和抗炎策略的临床试验进展迅速。

研究局限性和未来方向

研究局限性在于现有的生活方式干预研究缺乏大规模、长期的随机对照试验，且大部分证据主要来自高收入国家。未来的研究方向包括：

加强对多领域干预的临床试验。
进一步探索生物标志物的临床应用。
研究个体化的预防策略，以便在早期阶段对阿尔茨海默病进行干预。

参考文献

Survival in memory clinic cohort is short, even in young-onset dementia. - Hanneke Frederica Maria Rhodius-Meester;Betty M Tijms;Afina W Lemstra;Niels D Prins;Yolande A L Pijnenburg;Femke Bouwman;Philip Scheltens;Wiesje M van der Flier - Journal of neurology, neurosurgery, and psychiatry (2019)
Sodium oligomannate therapeutically remodels gut microbiota and suppresses gut bacterial amino acids-shaped neuroinflammation to inhibit Alzheimer's disease progression. - Xinyi Wang;Guangqiang Sun;Teng Feng;Jing Zhang;Xun Huang;Tao Wang;Zuoquan Xie;Xingkun Chu;Jun Yang;Huan Wang;Shuaishuai Chang;Yanxue Gong;Lingfei Ruan;Guanqun Zhang;Siyuan Yan;Wen Lian;Chen Du;Dabing Yang;Qingli Zhang;Feifei Lin;Jia Liu;Haiyan Zhang;Changrong Ge;Shifu Xiao;Jian Ding;Meiyu Geng - Cell research (2019)
Predicting clinical decline and conversion to Alzheimer's disease or dementia using novel Elecsys Aβ(1-42), pTau and tTau CSF immunoassays. - Kaj Blennow;Leslie M Shaw;Erik Stomrud;Niklas Mattsson;Jon B Toledo;Katharina Buck;Simone Wahl;Udo Eichenlaub;Valeria Lifke;Maryline Simon;John Q Trojanowski;Oskar Hansson - Scientific reports (2019)
Vascular dysfunction in the pathogenesis of Alzheimer's disease--A review of endothelium-mediated mechanisms and ensuing vicious circles. - Luigi Yuri Di Marco;Annalena Venneri;Eszter Farkas;Paul C Evans;Alberto Marzo;Alejandro F Frangi - Neurobiology of disease (2015)
High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. - Suzanne E Schindler;James G Bollinger;Vitaliy Ovod;Kwasi G Mawuenyega;Yan Li;Brian A Gordon;David M Holtzman;John C Morris;Tammie L S Benzinger;Chengjie Xiong;Anne M Fagan;Randall J Bateman - Neurology (2019)
Synaptic proteins in CSF as potential novel biomarkers for prognosis in prodromal Alzheimer's disease. - Flora H Duits;Gunnar Brinkmalm;Charlotte E Teunissen;Ann Brinkmalm;Philip Scheltens;Wiesje M Van der Flier;Henrik Zetterberg;Kaj Blennow - Alzheimer's research & therapy (2018)
Novel diagnostic cerebrospinal fluid biomarkers for pathologic subtypes of frontotemporal dementia identified by proteomics. - Charlotte E Teunissen;Naura Elias;Marleen J A Koel-Simmelink;Sisi Durieux-Lu;Arjan Malekzadeh;Thang V Pham;Sander R Piersma;Tommaso Beccari;Lieke H H Meeter;Elise G P Dopper;John C van Swieten;Connie R Jimenez;Yolande A L Pijnenburg - Alzheimer's & dementia (Amsterdam, Netherlands) (2016)
Effect of the Apolipoprotein E Genotype on Cognitive Change During a Multidomain Lifestyle Intervention: A Subgroup Analysis of a Randomized Clinical Trial. - Alina Solomon;Heidi Turunen;Tiia Ngandu;Markku Peltonen;Esko Levälahti;Seppo Helisalmi;Riitta Antikainen;Lars Bäckman;Tuomo Hänninen;Antti Jula;Tiina Laatikainen;Jenni Lehtisalo;Jaana Lindström;Teemu Paajanen;Satu Pajala;Anna Stigsdotter-Neely;Timo Strandberg;Jaakko Tuomilehto;Hilkka Soininen;Miia Kivipelto - JAMA neurology (2018)
In vivo cortical spreading pattern of tau and amyloid in the Alzheimer disease spectrum. - Hanna Cho;Jae Yong Choi;Mi Song Hwang;You Jin Kim;Hye Mi Lee;Hye Sun Lee;Jae Hoon Lee;Young Hoon Ryu;Myung Sik Lee;Chul Hyoung Lyoo - Annals of neurology (2016)
Plasma phospholipids identify antecedent memory impairment in older adults. - Mark Mapstone;Amrita K Cheema;Massimo S Fiandaca;Xiaogang Zhong;Timothy R Mhyre;Linda H MacArthur;William J Hall;Susan G Fisher;Derick R Peterson;James M Haley;Michael D Nazar;Steven A Rich;Dan J Berlau;Carrie B Peltz;Ming T Tan;Claudia H Kawas;Howard J Federoff - Nature medicine (2014)

引用本文的文献

Central Administration of Ampelopsin A Isolated from Vitis vinifera Ameliorates Cognitive and Memory Function in a Scopolamine-Induced Dementia Model. - Yuni Hong;Yun-Hyeok Choi;Young-Eun Han;Soo-Jin Oh;Ansoo Lee;Bonggi Lee;Rebecca Magnan;Shi Yong Ryu;Chun Whan Choi;Min Soo Kim - Antioxidants (Basel, Switzerland) (2021)
Repetitive transcranial magnetic stimulation increases the brain's drainage efficiency in a mouse model of Alzheimer's disease. - Yangyang Lin;Jian Jin;Rongke Lv;Yuan Luo;Weiping Dai;Wenchang Li;Yamei Tang;Yuling Wang;Xiaojing Ye;Wei-Jye Lin - Acta neuropathologica communications (2021)
Alzheimer's disease drug development pipeline: 2021. - Jeffrey Cummings;Garam Lee;Kate Zhong;Jorge Fonseca;Kazem Taghva - Alzheimer's & dementia (New York, N. Y.) (2021)
Who funds Alzheimer's disease drug development? - Jeffrey Cummings;Justin Bauzon;Garam Lee - Alzheimer's & dementia (New York, N. Y.) (2021)
Roles and Mechanisms of Gut Microbiota in Patients With Alzheimer's Disease. - Shaochang Wu;Xia Liu;Ruilai Jiang;Xiumei Yan;Zongxin Ling - Frontiers in aging neuroscience (2021)
From blood to brain: blood cell-based biomimetic drug delivery systems. - Yong-Jiang Li;Jun-Yong Wu;Jihua Liu;Xiaohan Qiu;Wenjie Xu;Tiantian Tang;Da-Xiong Xiang - Drug delivery (2021)
Formaldehyde and De/Methylation in Age-Related Cognitive Impairment. - Ting Li;Yan Wei;Meihua Qu;Lixian Mou;Junye Miao;Mengqi Xi;Ying Liu;Rongqiao He - Genes (2021)
Protein Aggregation Landscape in Neurodegenerative Diseases: Clinical Relevance and Future Applications. - Niccolò Candelise;Silvia Scaricamazza;Illari Salvatori;Alberto Ferri;Cristiana Valle;Valeria Manganelli;Tina Garofalo;Maurizio Sorice;Roberta Misasi - International journal of molecular sciences (2021)
Peptides Derived from Growth Factors to Treat Alzheimer's Disease. - Suzanne Gascon;Jessica Jann;Chloé Langlois-Blais;Mélanie Plourde;Christine Lavoie;Nathalie Faucheux - International journal of molecular sciences (2021)
Tau Seeding Mouse Models with Patient Brain-Derived Aggregates. - Aiko Robert;Michael Schöll;Thomas Vogels - International journal of molecular sciences (2021)

... (1887 更多篇文献)

Alzheimer's disease. ​

文献信息 ​

一句话小结 ​

在麦伴科研 (maltsci.com) 搜索更多文献 ​

摘要 ​

英文摘要 ​

麦伴智能科研服务 ​

主要研究问题 ​

核心洞察 ​

研究背景和目的 ​

主要方法/材料/实验设计 ​

关键结果和发现 ​

主要结论/意义/创新性 ​

研究局限性和未来方向 ​

参考文献 ​

引用本文的文献 ​