{"id":1584429,"date":"2022-08-02T09:36:02","date_gmt":"2022-08-02T13:36:02","guid":{"rendered":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/?p=1584429"},"modified":"2022-08-02T09:36:31","modified_gmt":"2022-08-02T13:36:31","slug":"is-the-basis-of-alzheimers-research-fundamentally-flawed","status":"publish","type":"post","link":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/is-the-basis-of-alzheimers-research-fundamentally-flawed\/","title":{"rendered":"Is the Basis of Alzheimer\u2019s Research Fundamentally Flawed?"},"content":{"rendered":"<aside class=\"mashsb-container mashsb-main mashsb-stretched\"><div class=\"mashsb-box\"><div class=\"mashsb-count mash-medium\" style=\"&quot;\"><div class=\"counts mashsbcount\">16<\/div><span class=\"mashsb-sharetext\">SHARES<\/span><\/div><div class=\"mashsb-buttons\"><a class=\"mashicon-facebook mash-medium mash-nomargin mashsb-noshadow\" href=\"https:\/\/www.facebook.com\/sharer.php?u=https%3A%2F%2Fwww.conservativenewsdaily.net%2Fbreaking-news%2Fis-the-basis-of-alzheimers-research-fundamentally-flawed%2F\" target=\"_top\" rel=\"nofollow\"><span class=\"icon\"><\/span><span class=\"text\">Facebook<\/span><\/a><a class=\"mashicon-twitter mash-medium mash-nomargin mashsb-noshadow\" href=\"https:\/\/twitter.com\/intent\/tweet?text=&amp;url=https:\/\/www.conservativenewsdaily.net\/breaking-news\/?p=1584429&amp;via=ConservNewsDly\" target=\"_top\" rel=\"nofollow\"><span class=\"icon\"><\/span><span class=\"text\">Twitter<\/span><\/a><a class=\"mashicon-subscribe mash-medium mash-nomargin mashsb-noshadow\" href=\"#\" target=\"_top\" rel=\"nofollow\"><span class=\"icon\"><\/span><span class=\"text\">Subscribe<\/span><\/a><div class=\"onoffswitch2 mash-medium mashsb-noshadow\" style=\"display:none\"><\/div><\/div>\n            <\/div>\n                <div style=\"clear:both\"><\/div><\/aside>\n            <!-- Share buttons by mashshare.net - Version: 4.0.47--><p>A new report found image tampering that could throw out years of research for a cure<\/p>\n<div>\n<p>Alzheimer\u2019s disease is a type of dementia. It is named after German pathologist Alois Alzheimer, who discovered what is believed to be the distinctive feature of the disease\u2013plaques and other protein deposits\u2013in the brain of a deceased patient in 1906.<\/p>\n<p>In the 1980s, a protein called amyloid beta (A\u03b2) was identified as the main component of the plaques. This led to the \u201camyloid hypothesis,\u201d which suggests that a primary cause of Alzheimer\u2019s disease is A\u03b2 clumps in brain tissue. The amyloid hypothesis, although controversial, has been the basis of most Alzheimer\u2019s disease research for decades.<\/p>\n<p>A recent analysis of the images in published papers discovered \u201cshockingly blatant\u201d examples of image tampering, according to a new <a href=\"https:\/\/www.science.org\/content\/article\/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease\">report<\/a> by Science. It implicates one of the foundations of amyloid based cures for Alzheimer\u2019s disease. The process of reaching this bombshell discovery has been fascinating, to say the least.<\/p>\n<h2>The Amyloid Hypothesis<\/h2>\n<p>In theory, stopping A\u03b2 deposits became the most plausible strategy to cure Alzheimer\u2019s. But no one had proved that any one of the many known A\u03b2 deposits (or oligomers) directly caused the disease. Hundreds of clinical trials failed to generate the expected results. This led more and more scientists to question the validity of the amyloid hypothesis.<\/p>\n<\/p>\n<p><noscript><img loading=\"lazy\" decoding=\"async\" class=\"alignleft size-full wp-image-4635295\" src=\"https:\/\/img.theepochtimes.com\/assets\/uploads\/2022\/08\/01\/56_clean-01.jpg\" alt=\"Epoch Times Photo\" width=\"8001\" height=\"8094\" \/><\/noscript><\/p>\n<p>In 2006, a <a href=\"https:\/\/www.nature.com\/articles\/nature04533\">groundbreaking study<\/a>, conducted by a team at the University of Minnesota (UMN) Twin Cities, identified an A\u03b2 subtype, A\u03b2*56, as the culprit that caused Alzheimer\u2019s dementia in rats.<\/p>\n<p>Like a beam of light piercing through the darkest night, this discovery cemented the dominance of the amyloid hypothesis in seeking a cure for Alzheimer\u2019s.<\/p>\n<p>The UMN study was done in the lab of Prof. Karen Ashe. A young French scientist, Sylvain Lesn\u00e9, who worked in the lab, was the first author of the paper. Lesn\u00e9 was 34 years old when the study was published in Nature. This seminal paper has been cited in almost 2,300 scholarly articles.<\/p>\n<p>The gist of the experiment involves 1) identifying a previously unknown oligomer species A\u03b2*56 in the brains of transgenic mice; 2) isolating A\u03b2*56 from the transgenic mice and injecting it into young mice; 3) observing the young mice\u2019s memory capacity plummeting over time.<\/p>\n<p>What\u2019s a transgenic mouse, you might ask? It was created by Karen Ashe in the mid-1990s. Inside a transgenic mouse\u2019s brain, human A\u03b2 is produced, which forms plaques. As a result, the mouse shows dementia-like symptoms.<\/p>\n<p>Since then, NIH has poured billions of dollars into research focused on A\u03b2*56.<\/p>\n<p>A lot of other investigators set off looking for A\u03b2*56-like oligomer species. But none of them were successful. The drug development based on the A\u03b2*56 discovery and amyloid hypothesis has been disappointing and controversial.<\/p>\n<h2>Controversies Surrounding Alzheimer\u2019s Drug Development<\/h2>\n<p>First, we have Aduhelm.<\/p>\n<p>In June 2021, Biogen\u2019s Aduhelm (aducanumab) became the first drug approved by the United States Food and Drug Administration (FDA) for the treatment of Alzheimer\u2019s in nearly 20 years.<\/p>\n<p>However, FDA\u2019s <a href=\"https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-grants-accelerated-approval-alzheimers-drug\">accelerated approval<\/a> was controversial, because of Aduhelm\u2019s questionable efficacy data and undesirable risk-benefit ratio. Only 29 patients enrolled in the study, when 6,000 were needed. And the insurers drastically limited their coverage of the drug. Eventually, Biogen <a href=\"https:\/\/www.biospace.com\/article\/biogen-abandons-real-world-study-of-alzheimer-s-drug-aduhelm\/\">abandoned<\/a> the <a href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05097131\">post-market real-world study<\/a> in June 2022.<\/p>\n<p>Then there is Simufilam.<\/p>\n<p>Simufilam, developed by Cassava Sciences, was also met with strong criticism. Matthew Schrag, a neuroscientist and physician at Vanderbilt University, found \u201capparently altered or duplicated images in dozens of journal articles\u201d about Simufilam. Schrag\u2019s findings were supported by independent image analysts and some Alzheimer\u2019s experts.<\/p>\n<p>His analysis was used in an August 2021 <a href=\"https:\/\/www.regulations.gov\/docket\/FDA-2021-P-0930\/document\">petition<\/a> to FDA to halt two phase 3 clinical trials of Simufilam. In February 2022, FDA refused the petition, calling it the wrong way to intervene.<\/p>\n<p>It\u2019s worth noting that Schrag\u2019s findings implicated senior management at Cassava Sciences, and prominent neurologists at City University of New York (CUNY) and Harvard University, who were advisors for Cassava.<\/p>\n<p>Several papers that contain questionable images have been retracted. Various investigations were triggered.<\/p>\n<p>But Schrag\u2019s research did not stop there, and it generated a bigger shockwave across the Alzheimer\u2019s research communities.<\/p>\n<h2>A Bombshell Discovery<\/h2>\n<p>In his analysis of images in published papers, Schrag inevitably came across papers by Lesn\u00e9, including the seminal paper from 2006.<\/p>\n<p>Shockingly, Schrag found signs of tampering in papers co-authored by Lesn\u00e9, including the images in the 2006 paper, the basis for many others.<\/p>\n<p>In January 2022, Schrag raised his doubts about A\u03b2*56 research with NIH. Meanwhile, Science conducted a six month investigation and published an elaborate <a href=\"https:\/\/www.science.org\/content\/article\/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease\">report<\/a> in July 2022. It provides strong support for Schrag\u2019s suspicions and raises questions about Lesn\u00e9\u2019s research.<\/p>\n<p>The authors of the <a href=\"https:\/\/www.nature.com\/articles\/nature04533\">2006 paper<\/a> \u201cappeared to have composed figures by piecing together parts of photos from different experiments,\u201d says Elisabeth Bik, a molecular biologist and well-known forensic image consultant. Bik reviewed Schrag\u2019s findings upon Science\u2019s request. They found more than 20 suspicious papers by Lesn\u00e9, and 10 of them are about A\u03b2*56.<\/p>\n<p>The Science <a href=\"https:\/\/www.science.org\/content\/article\/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease\">report<\/a> includes a detailed image showing duplicated bands.<\/p>\n<p>UMN is reviewing Lesn\u00e9\u2019s work. Ashe declined via email to be interviewed or to answer written questions posed by Science.<\/p>\n<p>The Science report also mentioned that in May 2022, four months after Schrag delivered his concerns to NIH, <a href=\"https:\/\/reporter.nih.gov\/search\/B0q-ZVTtnk6p4TZffENe1Q\/project-details\/10464632\">Lesn\u00e9 received a coveted R01 research project grant<\/a> from NIH, with up to five years of support. The NIH program officer for the grant, Austin Yang, was one of the co-authors on the 2006 Nature paper.<\/p>\n<p>Top Alzheimer\u2019s researcher John Forsayeth of the University of California, San Francisco, reviewed and agreed with Schrag\u2019s analysis, and said that the amyloid hypothesis is \u201cthe scientific equivalent of the Ptolemaic model of the Solar System,\u201d in which the Sun and planets rotate around Earth.<\/p>\n<p>The shock waves generated by Schrag\u2019s findings have not been pacified. Sixteen years of precious research efforts by scientists the world over might be for naught. Billions of NIH dollars might be wasted. Alzheimer\u2019s disease is still debilitating millions around the world. Perhaps it is time for our scientific communities to rethink their strategy.<\/p>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>A new report found image tampering that could throw out years of research for a cureAlzheimer\u2019s disease is a type of dementia. It is named after German pathologist Alois Alzheimer,<\/p>\n","protected":false},"author":1,"featured_media":1894422,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_mo_disable_npp":"","fifu_image_url":"https:\/\/cndimages.nyc3.digitaloceanspaces.com\/breaking-news\/wp-content\/uploads\/2021\/01\/IMG_2758-scaled-1.jpg","fifu_image_alt":"","footnotes":""},"categories":[],"tags":[],"class_list":["post-1584429","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry"],"fifu_image_url":"https:\/\/cndimages.nyc3.digitaloceanspaces.com\/breaking-news\/wp-content\/uploads\/2021\/01\/IMG_2758-scaled-1.jpg","_links":{"self":[{"href":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/wp-json\/wp\/v2\/posts\/1584429","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/wp-json\/wp\/v2\/comments?post=1584429"}],"version-history":[{"count":0,"href":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/wp-json\/wp\/v2\/posts\/1584429\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/wp-json\/wp\/v2\/media\/1894422"}],"wp:attachment":[{"href":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/wp-json\/wp\/v2\/media?parent=1584429"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/wp-json\/wp\/v2\/categories?post=1584429"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.conservativenewsdaily.net\/breaking-news\/wp-json\/wp\/v2\/tags?post=1584429"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}