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文献精选 > 近年高分"阿尔茨海默病"研究（IF≥30，近5年）

Alzheimer's disease associated with Down syndrome: a genetic form of dementia. ​

文献信息 ​

DOI10.1016/S1474-4422(21)00245-3
PMID34687637
期刊The Lancet. Neurology
影响因子45.5
JCR 分区Q1
发表年份2021
被引次数189
关键词唐氏综合症, 阿尔茨海默病, 早发性痴呆, 生物标志物, 治疗
文献类型Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review
ISSN1474-4422
页码930-942
期号20(11)
作者Juan Fortea, Shahid H Zaman, Sigan Hartley, Michael S Rafii, Elizabeth Head, Maria Carmona-Iragui

一句话小结 ​

唐氏综合症成年人面临高风险的早发性痴呆，且其诊断挑战重重，然而研究发现液体和影像生物标志物在该群体中具有良好的诊断性能。当前对唐氏综合症的深入研究有望为阿尔茨海默病的预防和治疗提供新的思路，进而惠及更广泛的人群。

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唐氏综合症 · 阿尔茨海默病 · 早发性痴呆 · 生物标志物 · 治疗

摘要 ​

患有唐氏综合症的成年人会出现阿尔茨海默病的神经病理特征，并且罹患早发性痴呆的风险极高，而早发性痴呆目前已成为该人群的主要死亡原因。由于缺乏在该人群中经过验证的诊断标准，加之症状常常被与唐氏综合症相关的智力障碍所掩盖，痴呆的诊断仍然面临临床挑战。在唐氏综合症患者中，液体和影像生物标志物显示出良好的诊断性能，并且与散发性和常染色体显性阿尔茨海默病相比，其变化的时间特征惊人地相似。最重要的是，目前没有治疗方法可以预防阿尔茨海默病，尽管唐氏综合症的成年人可能是进行阿尔茨海默病预防试验的最佳人群。对唐氏综合症的前所未有的研究活动正在迅速改变这一严峻局面，这将转化为能够惠及其他人群的疾病修饰疗法。

英文摘要 ​

Adults with Down syndrome develop the neuropathological hallmarks of Alzheimer's disease and are at very high risk of developing early-onset dementia, which is now the leading cause of death in this population. Diagnosis of dementia remains a clinical challenge because of the lack of validated diagnostic criteria in this population, and because symptoms are overshadowed by the intellectual disability associated with Down syndrome. In people with Down syndrome, fluid and imaging biomarkers have shown good diagnostic performances and a strikingly similar temporality of changes with respect to sporadic and autosomal dominant Alzheimer's disease. Most importantly, there are no treatments to prevent Alzheimer's disease, even though adults with Down syndrome could be an optimal population in whom to conduct Alzheimer's disease prevention trials. Unprecedented research activity in Down syndrome is rapidly changing this bleak scenario that will translate into disease-modifying therapies that could benefit other populations.

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主要研究问题 ​

  1. 在唐氏综合症患者中，阿尔茨海默病的早期症状与其他人群有何不同？
  2. 目前针对唐氏综合症患者阿尔茨海默病的研究进展如何，是否有新的治疗方案？
  3. 在唐氏综合症人群中，流体和影像学生物标志物的应用有哪些具体实例？
  4. 如何提高唐氏综合症患者阿尔茨海默病的诊断准确性，是否有新的诊断标准正在制定？
  5. 唐氏综合症与阿尔茨海默病之间的遗传机制有哪些重要的研究发现？

核心洞察 ​

研究背景和目的 ​

唐氏综合症成人群体面临着阿尔茨海默病的神经病理特征，并且早发性痴呆的风险极高，这已成为该人群的主要死亡原因。由于缺乏有效的诊断标准，痴呆的诊断仍然是一个临床挑战。此外，唐氏综合症相关的智力障碍常常掩盖了痴呆的症状。本文旨在探讨唐氏综合症患者中痴呆的诊断方法及其与阿尔茨海默病的相关性，并强调开展预防性研究的重要性。

主要方法/材料/实验设计 ​

本研究采用流体和影像学生物标志物评估唐氏综合症患者的痴呆风险，并与散发性和常染色体显性阿尔茨海默病进行比较。具体的研究方法包括：

  1. 流体生物标志物检测：评估脑脊液和血液中的生物标志物。
  2. 影像学评估：使用MRI和PET扫描来观察脑部变化。
  3. 临床评估：对患者进行认知功能测试，以识别痴呆的早期症状。

以下是研究的技术路线图：

Mermaid diagram

关键结果和发现 ​

  1. 生物标志物表现：流体和影像学生物标志物在唐氏综合症患者中显示出良好的诊断性能，与阿尔茨海默病的变化时间相似。
  2. 症状表现：唐氏综合症患者的痴呆症状与智力障碍的重叠使得早期诊断更加困难。
  3. 研究活跃性：近年来，针对唐氏综合症的研究活动显著增加，为疾病修饰疗法的开发提供了新的可能性。

主要结论/意义/创新性 ​

本文强调了唐氏综合症成人群体作为阿尔茨海默病预防试验的理想人群，尽管目前尚无有效的预防治疗。研究显示，流体和影像学生物标志物的结合可以有效识别早期痴呆，为未来的干预措施奠定了基础。此外，研究活动的增加有望推动疾病修饰疗法的开发，这些疗法不仅可以改善唐氏综合症患者的生活质量，也可能对其他人群产生积极影响。

研究局限性和未来方向 ​

  • 局限性：目前缺乏足够的临床试验数据来验证流体和影像学生物标志物的有效性。此外，研究中未能充分考虑唐氏综合症患者的个体差异。
  • 未来方向：建议开展大规模的临床试验，以验证生物标志物的诊断性能，并探索可能的预防性治疗。此外，需关注如何在临床实践中更好地整合这些诊断工具，以提高早期识别和干预的效率。

参考文献 ​

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  2. A prospective 20-year longitudinal follow-up of dementia in persons with Down syndrome. - M McCarron;P McCallion;E Reilly;P Dunne;R Carroll;N Mulryan - Journal of intellectual disability research : JIDR (2017)
  3. Intracerebral haemorrhage in Down syndrome: protected or predisposed? - Lewis Buss;Elizabeth Fisher;John Hardy;Dean Nizetic;Jurgen Groet;Laura Pulford;André Strydom - F1000Research (2016)
  4. Plasma neurofilament light chain in the presenilin 1 E280A autosomal dominant Alzheimer's disease kindred: a cross-sectional and longitudinal cohort study. - Yakeel T Quiroz;Henrik Zetterberg;Eric M Reiman;Yinghua Chen;Yi Su;Joshua T Fox-Fuller;Gloria Garcia;Andres Villegas;Diego Sepulveda-Falla;Marina Villada;Joseph F Arboleda-Velasquez;Edmarie Guzmán-Vélez;Clara Vila-Castelar;Brian A Gordon;Stephanie A Schultz;Hillary D Protas;Valentina Ghisays;Margarita Giraldo;Victoria Tirado;Ana Baena;Claudia Munoz;Silvia Rios-Romenets;Pierre N Tariot;Kaj Blennow;Francisco Lopera - The Lancet. Neurology (2020)
  5. Down syndrome, Alzheimer disease, and cerebral amyloid angiopathy: The complex triangle of brain amyloidosis. - María Carmona-Iragui;Laura Videla;Alberto Lleó;Juan Fortea - Developmental neurobiology (2019)
  6. Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. - C A Lemere;J K Blusztajn;H Yamaguchi;T Wisniewski;T C Saido;D J Selkoe - Neurobiology of disease (1996)
  7. Associations between biomarkers and age in the presenilin 1 E280A autosomal dominant Alzheimer disease kindred: a cross-sectional study. - Adam S Fleisher;Kewei Chen;Yakeel T Quiroz;Laura J Jakimovich;Madelyn Gutierrez Gomez;Carolyn M Langois;Jessica B S Langbaum;Auttawut Roontiva;Pradeep Thiyyagura;Wendy Lee;Napatkamon Ayutyanont;Liliana Lopez;Sonia Moreno;Claudia Muñoz;Victoria Tirado;Natalia Acosta-Baena;Anne M Fagan;Margarita Giraldo;Gloria Garcia;Matthew J Huentelman;Pierre N Tariot;Francisco Lopera;Eric M Reiman - JAMA neurology (2015)
  8. Clinical and EEG features of seizures in adults with down syndrome. - Stela Lefter;Daniel J Costello;Brian McNamara;Brian Sweeney - Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society (2011)
  9. Endocytic pathway abnormalities precede amyloid beta deposition in sporadic Alzheimer's disease and Down syndrome: differential effects of APOE genotype and presenilin mutations. - A M Cataldo;C M Peterhoff;J C Troncoso;T Gomez-Isla;B T Hyman;R A Nixon - The American journal of pathology (2000)
  10. The Alzheimer's Biomarker Consortium-Down Syndrome: Rationale and methodology. - Benjamin L Handen;Ira T Lott;Bradley T Christian;Nicole Schupf;Sid OBryant;Mark Mapstone;Anne M Fagan;Joseph H Lee;Dana Tudorascu;Mei-Cheng Wang;Elizabeth Head;William Klunk;Beau Ances;Florence Lai;Shahid Zaman;Sharon Krinsky-McHale;Adam M Brickman;H Diana Rosas;Annie Cohen;Howard Andrews;Sigan Hartley;Wayne Silverman; - Alzheimer's & dementia (Amsterdam, Netherlands) (2020)

引用本文的文献 ​

  1. Epilepsy in Down Syndrome: A Highly Prevalent Comorbidity. - Miren Altuna;Sandra Giménez;Juan Fortea - Journal of clinical medicine (2021)
  2. Development of treatments for Down syndrome. - Michael S Rafii - The Lancet. Neurology (2022)
  3. Cortical atrophy and amyloid and tau deposition in Down syndrome: A longitudinal study. - Concepcion Padilla;Victor Montal;Madeleine J Walpert;Young T Hong;Tim D Fryer;Jonathan P Coles;Franklin I Aigbirhio;Sigan L Hartley;Ann D Cohen;Dana L Tudorascu;Bradley T Christian;Benjamin L Handen;William E Klunk;Anthony J Holland;Shahid H Zaman - Alzheimer's & dementia (Amsterdam, Netherlands) (2022)
  4. Dissecting the clinical heterogeneity of early-onset Alzheimer's disease. - Daniel W Sirkis;Luke W Bonham;Taylor P Johnson;Renaud La Joie;Jennifer S Yokoyama - Molecular psychiatry (2022)
  5. Feasibility and Long-Term Compliance to Continuous Positive Airway Pressure Treatment in Adults With Down Syndrome, a Genetic Form of Alzheimer's Disease. - Sandra Giménez;Ariadna Farre;Fátima Morente;Laura Videla;Marta Gutiérrez;Susana Clos;Ana Fernández;Marta Blanco;Miren Altuna;Jordi Pegueroles;Amparo Asensio;Bessy Benejam;Mar Batista;Isabel Barroeta;Ana Fortuna;Juan Fortea;Mercedes Mayos - Frontiers in neuroscience (2022)
  6. The Hole-Board Test in Mutant Mice. - Robert Lalonde;Catherine Strazielle - Behavior genetics (2022)
  7. Commentary on Oeckl et al., "Serum Beta-Synuclein Is Higher in Down Syndrome and Precedes Rise of pTau181". - Elizabeth Head;Henrik Zetterberg - Annals of neurology (2022)
  8. Association of Alzheimer Disease With Life Expectancy in People With Down Syndrome. - Maria Florencia Iulita;Diana Garzón Chavez;Maria Klitgaard Christensen;Natalia Valle Tamayo;Oleguer Plana-Ripoll;Sonja A Rasmussen;Marta Roqué Figuls;Daniel Alcolea;Laura Videla;Isabel Barroeta;Bessy Benejam;Miren Altuna;Concepción Padilla;Jordi Pegueroles;Susana Fernandez;Olivia Belbin;María Carmona-Iragui;Rafael Blesa;Alberto Lleó;Alexandre Bejanin;Juan Fortea - JAMA network open (2022)
  9. Involvement of the HERV-derived cell-fusion inhibitor, suppressyn, in the fusion defects characteristic of the trisomy 21 placenta. - Jun Sugimoto;Danny J Schust;Tomomi Yamazaki;Yoshiki Kudo - Scientific reports (2022)
  10. Rodent Modeling of Alzheimer's Disease in Down Syndrome: In vivo and ex vivo Approaches. - Clíona Farrell;Paige Mumford;Frances K Wiseman - Frontiers in neuroscience (2022)

... (179 更多 篇文献)

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