Written by Jinho Kim '26
Edited by Josephine Chen '24
On June 7th, 2021, a new headline broke into the conversation of Alzheimer’s Disease: the FDA granted accelerated approval of Aduhelm. For the first time in 18 years, a new drug had been approved to treat Alzheimer’s disease, supposedly an exciting feat; however, responses from the public were more mixed than ever [2]. An article later surfaced revealing that an advisory panel for the FDA had strongly voted against the drug’s approval because of doubts in evidence proving Aduhelm’s efficacy [6]. While these concerns were unsuccessful in preventing the approval of Aduhelm, they point at the many questions and problems faced in the past of Alzheimer’s research and suggest how changes must be made in order to make progress in the future.
Research over the years has mainly been oriented toward the Amyloid Hypothesis of Alzheimer’s disease. Starting in 1984, the protein beta-amyloid (Aβ) was identified as the main component of plaques, which were linked to Alzheimer’s disease. Throughout the many research studies, scientists came to a general consensus on the prognosis of disease: a buildup of Aβ plaques is responsible for the dysfunction in neurons, causing dementia [4].
Following this logic, Aduhelm and hundreds of other therapeutic trials are targeting amyloid deposits to treat Alzheimer’s. Annually, billions of dollars are spent on dementia research, with a majority dedicated to Alzheimer’s disease [1]. Despite these efforts, such therapies have yielded very little promise, yet the Aβ hypothesis still dominates research and drug development [7]. Why is it that scientists’ efforts are not yielding appropriate results? The answer to this question leads us back to a critical research paper that threatens one of the most cited Alzheimer’s studies of this century.
In 2006, researcher Sylvain Lesné published an influential paper in Nature identifying a specific amyloid-β protein assembly in the brain that impairs memory. This work was substantial, as it pinpointed a key element of the controversial amyloid hypothesis, maintaining Aβ plaques as the primary cause of the illness [3]. Since then, Lesné has released many more papers and has become a prominent figure in the Alzheimer’s research community. Sixteen years later however, Dr Matthew Schrag, a neuroscientist and physician at Vanderbilt University, has gone back and pointed out issues of concern regarding this original study. His apprehension prompted a six-month investigation by Science journal and fellow scientists. By the end of his study, hundreds of images from Lesné’s papers surfaced, with several of them labeled as “shockingly blatant” examples of image tampering. These experts also suggest that the experimental results were changed to better fit Lesné’s hypothesis, manipulating the subsequent conclusions [4].
Issues like this are particularly concerning because of the widespread implications they have on the direction of research. For such a well known figure like Sylvian Lesné, other researchers using his results to design subsequent experiments may have been misled by his results. Dr Schrag also notes how difficult it is to reproduce experiments in this field, making it a huge concern when considering that data streams might not be reliable. It is thus essential for all researchers to have a heightened awareness of the validity of influential studies [4]. Unreliable results and misled studies may also lead to downstream effects, such as ineffective therapeutics like Aduhelm.
Despite such controversy, it is still important to note the many advancements made throughout the years. We have come a long way in understanding how Alzheimer’s disease works and progresses, and novel therapeutic techniques are being designed and tested everyday [5]. Science is an ever-developing field, and by recognizing errors and correcting mistakes like these, we learn to explore paths and take steps in the right direction.
References
1. Alzheimer’s Disease Facts and Figures [Internet]. Alzheimer’s Disease and Dementia. [cited 2022 Nov 13]. Available from: https://www.alz.org/alzheimers-dementia/facts-figures
2. Belluck P, Kaplan S, Robbins R. How an Unproven Alzheimer’s Drug Got Approved. The New York Times [Internet]. 2021 Jul 19 [cited 2022 Nov 13]; Available from: https://www.nytimes.com/2021/07/19/health/alzheimers-drug-aduhelm-fda.html
3. Lesné S, Koh MT, Kotilinek L, Kayed R, Glabe CG, Yang A, et al. A specific amyloid-β protein assembly in the brain impairs memory. Nature. 2006 Mar;440(7082):352–7.
4. Piller C. Potential fabrication in research images threatens key theory of Alzheimer’s disease [Internet]. Science. 2022 [cited 2022 Nov 13]. Available from: https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
5. Servick K. Alzheimer’s drug approved despite doubts about effectiveness [Internet]. Science. 2021 [cited 2022 Nov 13]. Available from: https://www.science.org/content/article/alzheimer-s-drug-approved-despite-doubts-about-effectiveness
6. Sutton S. Addressing the Aduhelm Controversy [Internet]. The Medicine Maker. 2022 [cited 2022 Nov 13]. Available from: https://themedicinemaker.com/business-regulation/addressing-the-aduhelm-controversy
7. Woloshin S, Kesselheim AS. What to Know About the Alzheimer Drug Aducanumab (Aduhelm). JAMA Internal Medicine. 2022 Aug 1;182(8):892.
[Image] Colorful vector illustration of scientists researching brain and psychology of human on blue background [Internet]. Shutterstock [cited 2022 Nov 13]. Available from: https://www.shutterstock.com/image-vector/colorful-vector-illustration-scientists-researching-brain-1188871114