MaltSci 麦伴科研

Appearance

文献精选 > 高引权威"阿尔茨海默病"文献

Autosomal-dominant Alzheimer's disease: a review and proposal for the prevention of Alzheimer's disease. ​

文献信息 ​

DOI10.1186/alzrt59
PMID21211070
期刊Alzheimer's research & therapy
影响因子7.6
JCR 分区Q1
发表年份2011
被引次数292
关键词常染色体显性遗传, 阿尔茨海默病, 临床试验
文献类型Journal Article
页码1
期号3(1)
作者Randall J Bateman, Paul S Aisen, Bart De Strooper, Nick C Fox, Cynthia A Lemere, John M Ringman, Stephen Salloway, Reisa A Sperling, Manfred Windisch, Chengjie Xiong

一句话小结 ​

本综述探讨了常染色体显性遗传的阿尔茨海默病的临床、病理和分子研究，揭示了其与散发性阿尔茨海默病的相似性与差异，并介绍了相关的最新进展和临床试验倡议。研究结果对理解疾病机制、优化治疗时机及推动阿尔茨海默病预防具有重要意义。

在麦伴科研 (maltsci.com) 搜索更多文献 ​

常染色体显性遗传 · 阿尔茨海默病 · 临床试验

摘要 ​

常染色体显性遗传的阿尔茨海默病为我们提供了对阿尔茨海默病病理生理学的重要理解。本综述总结了常染色体显性阿尔茨海默病的临床、病理、影像学、生化和分子研究，强调了显性遗传形式的阿尔茨海默病与更常见的散发性阿尔茨海默病之间的相似性和差异。目前在常染色体显性阿尔茨海默病领域的最新进展也被介绍，包括国际显性遗传阿尔茨海默病网络及其临床试验倡议。常染色体显性阿尔茨海默病的临床试验可能会检验淀粉样蛋白假说，确定治疗时机，并为阿尔茨海默病的预防铺平道路。

英文摘要 ​

Autosomal-dominant Alzheimer's disease has provided significant understanding of the pathophysiology of Alzheimer's disease. The present review summarizes clinical, pathological, imaging, biochemical, and molecular studies of autosomal-dominant Alzheimer's disease, highlighting the similarities and differences between the dominantly inherited form of Alzheimer's disease and the more common sporadic form of Alzheimer's disease. Current developments in autosomal-dominant Alzheimer's disease are presented, including the international Dominantly Inherited Alzheimer Network and this network's initiative for clinical trials. Clinical trials in autosomal-dominant Alzheimer's disease may test the amyloid hypothesis, determine the timing of treatment, and lead the way to Alzheimer's disease prevention.

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 ​

  1. 如何评估常染色体显性阿尔茨海默病与散发性阿尔茨海默病在临床表现上的不同？
  2. 在预防阿尔茨海默病方面，是否有新的生物标志物正在被研究以预测疾病进展？
  3. 国际显性遗传阿尔茨海默病网络的临床试验具体针对哪些治疗策略或干预措施？
  4. 除了淀粉样蛋白假说，是否还有其他理论在解释显性遗传阿尔茨海默病的发病机制中发挥作用？
  5. 在阿尔茨海默病的预防研究中，如何确定最佳的治疗时机和干预措施的实施时间？

核心洞察 ​

研究背景和目的 ​

阿尔茨海默病（AD）是全球影响约2400万人的疾病，预计到2040年将增加到8000万。现有的治疗方法有限，迫切需要开发更有效的治疗方案。自发性阿尔茨海默病（SAD）是最常见的类型，而常染色体显性遗传的阿尔茨海默病（ADAD）则提供了对该疾病病理生理学的深刻理解。本研究综述了ADAD的临床、病理、影像、生化和分子研究，探讨ADAD与SAD的相似性和差异性，并提出了预防AD的可能性。

主要方法/材料/实验设计 ​

本研究主要采用文献综述的方法，整合了多项临床试验、遗传研究和生物标志物分析的数据。以下是研究的技术路线：

Mermaid diagram

关键结果和发现 ​

  • 临床表现：ADAD患者通常在30到50岁之间发病，表现出与SAD相似的认知功能下降，但ADAD的发病年龄显著更早。
  • 病理特征：ADAD的神经病理变化与SAD相似，包括神经元丧失、神经纤维缠结和淀粉样斑块。
  • 生物标志物：ADAD患者的脑脊液中Aβ42水平显著降低，tau和磷酸化tau水平增加，与SAD的生物标志物特征相似。
  • 影像学变化：MRI和PET研究显示，ADAD患者在临床症状出现前，已有显著的海马萎缩和代谢异常。

主要结论/意义/创新性 ​

本研究强调了ADAD在理解阿尔茨海默病病理生理学中的重要性，并提出了基于ADAD的预防策略。这些策略不仅可能延缓症状出现，还可能为更广泛的阿尔茨海默病治疗提供指导。ADAD的研究为开发早期干预措施提供了可能性，有助于提高患者及其家庭的生活质量。

研究局限性和未来方向 ​

  • 局限性：ADAD患者群体相对较小，研究结果可能无法广泛适用于所有AD患者。此外，现有的治疗试验仍处于早期阶段，缺乏大规模临床试验的数据支持。
  • 未来方向：建议未来研究应集中于大规模临床试验的设计，以评估针对ADAD的干预措施的有效性。同时，应加强对生物标志物的探索，以便更好地理解AD的进展机制。

通过深入研究ADAD，未来可能会为预防和治疗阿尔茨海默病提供新的视角和策略。

参考文献 ​

  1. The natural history of Alzheimer disease: a longitudinal presymptomatic and symptomatic study of a familial cohort. - Alison K Godbolt;Lisa Cipolotti;Hilary Watt;Nick C Fox;John C Janssen;Martin N Rossor - Archives of neurology (2004)
  2. Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. - A Goate;M C Chartier-Harlin;M Mullan;J Brown;F Crawford;L Fidani;L Giuffra;A Haynes;N Irving;L James - Nature (1991)
  3. Novel presenilin 1 mutation (S170F) causing Alzheimer disease with Lewy bodies in the third decade of life. - B Joy Snider;Joanne Norton;Mary A Coats;Sumi Chakraverty;Craig E Hou;Ramiro Jervis;Corinne L Lendon;Alison M Goate;Daniel W McKeel;John C Morris - Archives of neurology (2005)
  4. Beta-amyloid precursor protein mutants respond to gamma-secretase modulators. - Richard M Page;Amelie Gutsmiedl;Akio Fukumori;Edith Winkler;Christian Haass;Harald Steiner - The Journal of biological chemistry (2010)
  5. Carbon 11-labeled pittsburgh compound B positron emission tomographic amyloid imaging in patients with APP locus duplication. - Anne M Remes;Lauri Laru;Hannu Tuominen;Sargo Aalto;Nina Kemppainen;Helinä Mononen;Kjell Någren;Riitta Parkkola;Juha O Rinne - Archives of neurology (2008)
  6. APP locus duplication causes autosomal dominant early-onset Alzheimer disease with cerebral amyloid angiopathy. - Anne Rovelet-Lecrux;Didier Hannequin;Gregory Raux;Nathalie Le Meur;Annie Laquerrière;Anne Vital;Cécile Dumanchin;Sébastien Feuillette;Alexis Brice;Martine Vercelletto;Frédéric Dubas;Thierry Frebourg;Dominique Campion - Nature genetics (2006)
  7. Distinguishable effects of presenilin-1 and APP717 mutations on amyloid plaque deposition. - K Ishii;C Lippa;T Tomiyama;F Miyatake;K Ozawa;A Tamaoka;T Hasegawa;P E Fraser;S Shoji;L E Nee;D A Pollen;P H St George-Hyslop;K Ii;T Ohtake;R N Kalaria;M N Rossor;P L Lantos;N J Cairns;L A Farrer;H Mori - Neurobiology of aging (2001)
  8. The impact of different presenilin 1 andpresenilin 2 mutations on amyloid deposition, neurofibrillary changes and neuronal loss in the familial Alzheimer's disease brain: evidence for other phenotype-modifying factors. - T Gómez-Isla;W B Growdon;M J McNamara;D Nochlin;T D Bird;J C Arango;F Lopera;K S Kosik;P L Lantos;N J Cairns;B T Hyman - Brain : a journal of neurology (1999)
  9. Familial Alzheimer's disease-linked presenilin 1 variants elevate Abeta1-42/1-40 ratio in vitro and in vivo. - D R Borchelt;G Thinakaran;C B Eckman;M K Lee;F Davenport;T Ratovitsky;C M Prada;G Kim;S Seekins;D Yager;H H Slunt;R Wang;M Seeger;A I Levey;S E Gandy;N G Copeland;N A Jenkins;D L Price;S G Younkin;S S Sisodia - Neuron (1996)
  10. Effects of risk genes on BOLD activation in presymptomatic carriers of familial Alzheimer's disease mutations during a novelty encoding task. - John M Ringman;Luis D Medina;Meredith Braskie;Yaneth Rodriguez-Agudelo;Daniel H Geschwind;Miguel A Macias-Islas;Jeffrey L Cummings;Susan Bookheimer - Cerebral cortex (New York, N.Y. : 1991) (2011)

引用本文的文献 ​

  1. Alzheimer's disease: the challenge of the second century. - David M Holtzman;John C Morris;Alison M Goate - Science translational medicine (2011)
  2. Should persons with autosomal dominant AD be included in clinical trials? - Joshua D Grill;John M Ringman - Alzheimer's research & therapy (2011)
  3. Intracellular APP Domain Regulates Serine-Palmitoyl-CoA Transferase Expression and Is Affected in Alzheimer's Disease. - Marcus O W Grimm;Sven Grösgen;Tatjana L Rothhaar;Verena K Burg;Benjamin Hundsdörfer;Viola J Haupenthal;Petra Friess;Ulrike Müller;Klaus Fassbender;Matthias Riemenschneider;Heike S Grimm;Tobias Hartmann - International journal of Alzheimer's disease (2011)
  4. Cerebral microbleeds in familial Alzheimer's disease. - Natalie S Ryan;António J Bastos-Leite;Jonathan D Rohrer;David J Werring;Nick C Fox;Martin N Rossor;Jonathan M Schott - Brain : a journal of neurology (2012)
  5. Defining and describing the pre-dementia stages of familial Alzheimer's disease. - Natalie S Ryan;Martin N Rossor - Alzheimer's research & therapy (2011)
  6. Alzheimer's Prevention Initiative: a plan to accelerate the evaluation of presymptomatic treatments. - Eric M Reiman;Jessica B S Langbaum;Adam S Fleisher;Richard J Caselli;Kewei Chen;Napatkamon Ayutyanont;Yakeel T Quiroz;Kenneth S Kosik;Francisco Lopera;Pierre N Tariot - Journal of Alzheimer's disease : JAD (2011)
  7. Alzheimer's disease clinical trials: changing the paradigm. - Jeffrey L Cummings - Current psychiatry reports (2011)
  8. PET amyloid-beta imaging in preclinical Alzheimer's disease. - Andrei G Vlassenko;Tammie L S Benzinger;John C Morris - Biochimica et biophysica acta (2012)
  9. Testing the right target and right drug at the right stage. - Reisa A Sperling;Clifford R Jack;Paul S Aisen - Science translational medicine (2011)
  10. Brain imaging in the study of Alzheimer's disease. - Eric M Reiman;William J Jagust - NeuroImage (2012)

... (282 更多 篇文献)

© 2025 MaltSci 麦伴科研 - 我们用人工智能技术重塑科研