The so-called "amyloid cascade hypothesis" provides an elegant explanation of Alzheimer's disease (AD), has motivated the amyloid-lowering therapeutic strategy, and led to the elaboration of a rich experimental and conceptual toolkit for the field to progress. But it might be incorrect. The scientific evidence base supporting the efficacy and safety of current anti-amyloid antibody treatments in AD is weak. Nevertheless, we argue that there is a bias towards the amyloid-lowering therapeutic strategy amongst key opinion leaders in the research and advocacy communities. To demonstrate this, we first focus on the AD lexicon: while any accrual of amyloid on a brain PET scan can now permit diagnosis/definition of AD, lowering positron emission tomography (PET) amyloid is considered disease modification, and treatment-induced side-effects are hidden behind neutral-sounding acronyms: ARIA (amyloid-β (Aβ)-related imaging abnormalities: brain bleeding and swelling) and ARPA (amyloid-β (Aβ) removal-related pseudo-atrophy: brain shrinkage). Second, we underline that drugmakers did not test anti-amyloid antibodies against the best proven interventions and did not adequately inform trial participants of risks, thus violating research ethics of the Declaration of Helsinki on 2 counts. In conclusion, we are critical of over-reliance on the idea that PET amyloid-lowering treatments for AD are a therapeutic revolution as claimed, and consider that optimism does not excuse a lack of scientific, regulatory, and ethical integrity. We argue for rigorous, properly controlled (e.g. donepezil) anti-amyloid trials demonstrating cognitive and functional benefit before accepting amyloid-lowering drugs as the new standard of care for AD patients.

Timothy Daly

Andi Olluri

Markku Kurkinen

Advances in Clinical and Experimental Medicine

弗罗茨瓦夫医科大学自 1992 年以来一直在出版临床和实验医学进展。建立医学期刊是心脏病学系主任 BOGUMIŁ HALAWA 教授的想法，并得到了弗罗茨瓦夫医科大学校长教授的全力支持。 . ZBIGNIEW KNAPIK。 HALAWA 教授也是 1992-1997 年间的第一任主编。该杂志的标题为“POSTĘPY MEDYCYNY KLINICZNEJ I DOŚWIADCZALNEJ”，每季度出版一次。 LESZEK PARADOWSKI 于 1997 年至 1999 年担任主编。 1998年，他开始修改期刊的简介和封面设计，并被编辑委员会接受。标题改为临床和实验医学进展。欢迎发表英文文章。新成立的国际编辑部邀请了多位波兰国内外医学界的杰出代表参加。 ANTONINA HARŁOZIŃSKA-SZMYRKA 在 2000-2005 年担任主编，在 2006-2007 年再次担任教授。 LESZEK PARADOWSKI 和教授。 MARIA PODOLAK-DAWIDZIAK 在 2008-2016 年担任主编。自 2017 年起，主编为教授。 MACIEJ BAGŁAJ。自 2005 年 7 月以来，原始论文仅以英文发表。不再接受病例报告。稿件由两名独立审稿人和一名统计审稿人审阅，英文文本由母语人士校对。该期刊已被多个数据库索引：SCOPUS、ULRICH'S 国际期刊目录、哥白尼索引，自 2007 年以来在汤森路透数据库中：SCIENCE CITATION INDEX EXPANDED I JOURNAL CITATION REPORTS/SCIENCE EDITION。2010 年该期刊获得了影响因子，现在是1.179 分。该期刊发表的文章在波兰科学研究委员会中获得15分，在哥白尼索引中获得169.43分。自2012年11月7日起，《临床与实验医学进展》被国家图书馆收录。医学的 MEDLINE 数据库。期刊中印刷的英文摘要包含在内，可使用 PUBMED HTTP://WWW.NCBI.NLM.NIH.GOV/PUBMED 进行搜索。

Advances in Clinical and Experimental Medicine has been published by the Wrocław Medical University since 1992, focusing on advancements in clinical and experimental medicine. The establishment of this journal was initiated by Professor BOGUMIŁ HALAWA, the head of the Department of Cardiology, with full support from the university president, Professor ZBIGNIEW KNAPIK. Professor HALAWA served as the first editor-in-chief from 1992 to 1997. The journal was initially titled "POSTĘPY MEDYCYNY KLINICZNEJ I DOŚWIADCZALNEJ" and is published quarterly. LESZEK PARADOWSKI served as editor-in-chief from 1997 to 1999 and modified the journal's profile and cover design in 1998, which was accepted by the editorial board, leading to the title change to Advances in Clinical and Experimental Medicine. The journal welcomes submissions of articles in English and has established an international editorial board, inviting distinguished representatives from the Polish and international medical community. ANTONINA HARŁOZIŃSKA-SZMYRKA served as editor-in-chief from 2000 to 2005 and again from 2006 to 2007. LESZEK PARADOWSKI and Professor MARIA PODOLAK-DAWIDZIAK served as editors from 2008 to 2016. Since 2017, the editor-in-chief has been Professor MACIEJ BAGŁAJ. Since July 2005, only original papers in English are accepted, and case reports are no longer accepted. Manuscripts are reviewed by two independent reviewers and one statistical reviewer, and the English text is proofread by native speakers. The journal is indexed in several databases, including SCOPUS, ULRIH'S International Journal Directory, and the Copernicus Index, and has been included in the Thomson Reuters database since 2007, under the SCIENCE CITATION INDEX EXPANDED and JOURNAL CITATION REPORTS/SCIENCE EDITION. In 2010, the journal received an impact factor, currently at 1.179. Articles published in the journal receive 15 points from the Polish Science Research Committee and 169.43 points in the Copernicus Index. Since November 7, 2012, Advances in Clinical and Experimental Medicine has been included in the MEDLINE database of the National Library. The printed English abstracts in the journal can be searched via PUBMED at http://www.ncbi.nlm.nih.gov/pubmed.

《Advances in Clinical and Experimental Medicine》是弗罗茨瓦夫医科大学自1992年起出版的期刊，专注于临床和实验医学的进展。该期刊的创办源于心脏病学系主任BOGUMIŁ HALAWA教授的构想，并得到了校长ZBIGNIEW KNAPIK教授的全力支持。HALAWA教授是1992年至1997年的首任主编。期刊最初的标题为“POSTĘPY MEDYCYNY KLINICZNEJ I DOŚWIADCZALNEJ”，每季度出版一次。LESZEK PARADOWSKI于1997年至1999年担任主编，并于1998年对期刊的简介和封面设计进行了修改，得到了编辑委员会的认可，标题也随之改为《Advances in Clinical and Experimental Medicine》。该期刊欢迎英文文章的投稿，并成立了国际编辑部，邀请了多位波兰及国际医学界的杰出代表参与编辑工作。ANTONINA HARŁOZIŃSKA-SZMYRKA在2000年至2005年担任主编，并于2006年至2007年再次担任此职务。LESZEK PARADOWSKI和MARIA PODOLAK-DAWIDZIAK教授在2008年至2016年期间担任主编。自2017年起，主编为MACIEJ BAGŁAJ教授。自2005年7月起，期刊仅接受英文原始论文的投稿，不再接受病例报告。所有稿件均由两名独立审稿人和一名统计审稿人进行评审，英文文本由母语人士校对。该期刊已被多个数据库索引，包括SCOPUS、ULRICH'S国际期刊目录和哥白尼索引，自2007年起被汤森路透数据库收录，属于SCIENCE CITATION INDEX EXPANDED和JOURNAL CITATION REPORTS/SCIENCE EDITION。2010年，该期刊获得了影响因子，目前为1.179分。期刊发表的文章在波兰科学研究委员会中获得15分，在哥白尼索引中获得169.43分。自2012年11月7日起，《Advances in Clinical and Experimental Medicine》被国家图书馆收录于医学的MEDLINE数据库。期刊中印刷的英文摘要可通过PUBMED（http://www.ncbi.nlm.nih.gov/pubmed）进行搜索。

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医学, 医学研究与实验	4

Anti-amyloid treatments in Alzheimer’s disease: elegance, evidence and ethics

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MEDICINE, RESEARCH & EXPERIMENTAL	3