Appearance
Alzheimer's disease.
Literature Information
| DOI | 10.1016/S0140-6736(20)32205-4 |
|---|---|
| PMID | 33667416 |
| Journal | Lancet (London, England) |
| Publication Year | 2021 |
| Times Cited | 1897 |
| Keywords | Alzheimer's disease, biomarkers, genetic risk, cognitive prevention, pharmacological treatment |
| Literature Type | Journal Article, Review |
| ISSN | 0140-6736 |
| Pages | 1577-1590 |
| Issue | 397(10284) |
| Authors | Philip Scheltens, Bart De Strooper, Miia Kivipelto, Henne Holstege, Gael Chételat, Charlotte E Teunissen, Jeffrey Cummings, Wiesje M van der Flier |
TL;DR
This seminar reviews significant advancements in Alzheimer's disease research, highlighting that by 2050, dementia prevalence is expected to triple globally, with genetic factors playing a crucial role in risk. It emphasizes the importance of emerging biomarkers for diagnosis and the potential of lifestyle interventions and novel pharmacological treatments currently in clinical trials to mitigate Alzheimer's disease impact.
Search for more papers on MaltSci.com
Alzheimer's disease · biomarkers · genetic risk · cognitive prevention · pharmacological treatment
Abstract
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.
MaltSci.com AI Research Service
Intelligent ReadingAnswer any question about the paper and explain complex charts and formulas
Locate StatementsFind traces of a specific claim within the paper
Add to KBasePerform data extraction, report drafting, and advanced knowledge mining
Primary Questions Addressed
- What are the latest advancements in pharmacological treatments for Alzheimer's disease?
- How do genetic factors influence the risk of developing Alzheimer's disease in different populations?
- What role do lifestyle modifications play in the management and prevention of Alzheimer's disease?
- Can you explain the significance of novel biomarkers like PET scans and plasma assays in the early detection of Alzheimer's disease?
- How does the biological definition of Alzheimer's disease impact prevalence estimates compared to clinical definitions?
Key Findings
Research Background and Purpose
Alzheimer's disease (AD) is the leading cause of dementia and poses a significant global health challenge. The prevalence of dementia is projected to double in Europe and triple worldwide by 2050. This seminar aims to provide an updated overview of the developments in AD research, including advances in understanding its pathology, genetic factors, diagnostic criteria, and treatment options.
Main Methods/Materials/Experimental Design
The authors conducted a comprehensive literature review, focusing on studies published between 2010 and 2020. They utilized databases such as the Cochrane Library, PubMed, and Embase, using search terms related to Alzheimer's disease, including "pathology," "diagnosis," and "biomarkers." The search was complemented by reviewing reference lists of relevant articles.
Key Results and Findings
- Pathophysiology: The early cellular phase of AD involves amyloid β accumulation, leading to tau pathology. More than 40 genetic risk loci have been identified, with APOE ε4 being the most significant.
- Biomarkers: New biomarkers such as PET scans and plasma assays for amyloid β and phosphorylated tau have shown promise for both clinical and research applications.
- Prevention Trials: Multidomain lifestyle interventions have demonstrated cognitive benefits in high-risk populations, suggesting that lifestyle factors can positively influence outcomes, even if they do not directly alter AD pathology.
- Pharmacological Treatments: Advanced trials are underway for anti-amyloid β, anti-tau, and anti-inflammatory strategies, showing potential for modifying disease progression.
Main Conclusions/Significance/Innovation
The seminar highlights the importance of early diagnosis and intervention in AD. The evolving ATN (Amyloid, Tau, Neurodegeneration) framework allows for the biological definition of AD, emphasizing the role of biomarkers in early diagnosis. The findings underscore the potential for lifestyle interventions and pharmacological treatments to alter the disease trajectory, paving the way for more personalized approaches in AD management.
Research Limitations and Future Directions
- Limitations: The reliance on clinical and biological definitions may overlook other dementia causes, particularly vascular contributions. There are operational challenges in implementing the ATN framework in clinical practice.
- Future Directions: Ongoing research is needed to refine diagnostic criteria, explore the interactions between lifestyle and genetic factors, and develop comprehensive treatment strategies that combine pharmacological and non-pharmacological interventions. The establishment of global networks, such as the World Wide FINGERS network, aims to optimize prevention strategies across diverse populations.
| Section | Summary |
|---|---|
| Research Background | Alzheimer’s disease prevalence is rising, necessitating updated insights into its management. |
| Methods | Comprehensive literature review of recent studies on AD pathology, genetics, and treatments. |
| Key Findings | Identified biomarkers, genetic risk factors, and the efficacy of lifestyle interventions. |
| Conclusions | Early diagnosis and multimodal treatment strategies are essential for effective AD management. |
| Limitations and Future Work | Need for improved diagnostic frameworks and ongoing research into personalized prevention. |
References
- 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)
Literatures Citing This Work
- 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 more literatures)
© 2025 MaltSci - We reshape scientific research with AI technology