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Writer's pictureThe Pre-Collegiate Global Health Review

Leading Alzheimer’s Theory Questioned: What Does this Mean for the Future?

Megan Lee, Plainview-Old Bethpage John F. Kennedy High School, Plainview, New York, USA 


Summary

As the world’s population is quickly aging, scientists expect a large increase of Alzheimer’s disease (AD) cases, making it an alarming health concern. Comparisons of the prevalence of AD worldwide indicate that Western countries show the greatest incidence of Alzheimer’s, but eastern countries are catching up (Qiu et al., 2009). Experts emphasize the need for a usable treatment for AD, which would help societies from all over. A 2006 study supporting the amyloid hypothesis gave hope to all, and set a path for future AD research. However, in 2022, the 2006 study was proven to have altered images, shocking the science world. Scientists believe that time and resources were wasted on unsuccessful trials that were based on the results of the 2006 study. However, the Alzheimer’s research community is looking towards the future, researching different hypotheses and working together to ensure patients can get a treatment or even a cure.


By 2030, the population of people aged 60 and older will reach 1.4 billion, with 1 in 6 people fitting the age category (WHO, 2022). As the worldwide aging population rapidly grows, Alzheimer’s disease (AD) has become an increasing health concern. Due to its prevalence, nations have mobilized to track the disease’s effect within their populations. A study analyzing data from the 2019 Global Burden of Disease database unveiled that from 1990 to 2019, the incidence of Alzheimer’s disease has increased from 147.95% to 160.84% (Li, 2022). A comparison of the prevalence of AD worldwide indicates that Western countries are those affected the greatest by the extensiveness of Alzheimer’s. In the West, 60% of dementia cases are Alzheimer's, making it the most common type of dementia (Rizzi et al., 2014).  


Figure 1 Exhibits age-specific incidence of AD per 1000 persons across continents and countries


As seen in Figure 1, the U.S. has the greatest number of AD cases per 1000 people in all age divisions, however, for all locations, there are the most incidences at 85-89. (Qiu et al., 2009). To further understand the impact of Alzheimer’s, it is essential to examine the economic effect AD has on society. In 2020, the estimated total cost of treatment for AD (worldwide) was $305 billion, but as the population ages, the cost will pass $1 trillion (Wong, 2020). Experts say that advances in strategies that could lead to a 1-year delay in the onset and progression of AD would significantly reduce the disease’s global burden (Qiu et al., 2009), adding to the importance of research that could treat or cure Alzheimer’s disease. After data in an influential study in AD research was shown to be falsified, the research world was shaken. As a result, it is crucial to identify how Alzheimer’s research and patients were affected and how the Alzheimer’s community will advance.


Sylvain Lesné, a professor of neuroscience, was the key author in a 2006 Nature study that identified a possible cause of Alzheimer’s. For nearly 16 years, the study influenced how researchers would investigate AD and determined how research grants were given (Lucchesi, 2022). Data from Lesné’s study supported the controversial amyloid hypothesis of AD, which states that amyloid-β plaques in brain tissue are primarily responsible for AD (Piller, 2022), and AD progression could be slowed if plaques were controlled (Lucchesi, 2022). This had given hope to researchers and set a path for the future of the disease. In July 2022, Charles Piller, an investigative journalist at Science, published a shocking article exposing altered images in the influential 2006 study. The exposé began with how neuroscientist and physician, Matthew Schrag discovered the altered images. Schrag was tasked with studying the science of the controversial Alzheimer’s drug, Simufilam. During his investigation, Schrag found altered images in multiple papers, including the 2006 paper from Lesné. Schrag partnered with Science Magazine and found approximately 70 altered images in Lesné’s paper. (Piller, 2022). Elisabeth Bik, a forensic image consultant, said the authors [of the papers] "appeared to have composed figures by piecing together parts of photos from different experiments.” Bik further comments that the results gathered from the experiment may have been undesirable and were changed to fit the hypothesis. (Piller, 2022).  

 

Lesné's paper was a landmark study; cited in ~2,300 scholarly articles and responsible for the rise in annual NIH support for studies labeled “amyloid, oligomer, and Alzheimer’s” (Piller, 2022). As a result, the science community was shocked when Piller's Science article was published. Due to Lesné’s paper, AD research was hyper-focused on the amyloid hypothesis. Thus, research not based on the hypothesis was dismissed (Lucchesi, 2022). Dr. Sara Imarisio, the head of research at Alzheimer’s Research UK, says if the images in Lesné’s paper were altered, then groups that have planned experiments on the results may have diverted valuable time (Pelc, 2022). Schrag hopes that from this experience, researchers will not solely focus on one hypothesis and instead study other possibilities so new discoveries can be made.  

 

People with AD are the biggest stakeholders in this conversation. Many treatments created were based on the science from Lesné’s results, and every Alzheimer’s trial has failed. After Lesné’s altered images were exposed, some experts attributed these trial failures to treatments that were focused on attacking the formation of amyloid-β, which may not be the primary cause of degeneration associated with Alzheimer’s (Lowe, 2022). The Alzheimer’s drug, Aducanumab, made to reduce amyloid-β plaques, was unsuccessful in trial, and scientists are now questioning whether attacking the plaques is the answer. Another trial for the drug, lecanemab, also attacking amyloid plaques was unsuccessful (MacMillan, 2023). Trials for lecanemab were international and held in the United States, Japan, and Sweden. Treatments not focused on attacking the amyloid-β protein could have been denied funding. Now, patients must wait for these treatments to gain funding, slowing the fight for a cure. However, the future is bright. Researchers around the world are showing no signs of stopping their work on Alzheimer’s Disease, with many research laboratories advocating for greater collaboration between countries to find a solution together.  


References

Bowlby, B. (2022, September 22). Most cited and most notorious: How the 2006 alzheimer’s paper potentially misled research. BioTechniques. https://www.biotechniques.com/neuroscience/most-cited-and-most-notorious-how-the-2006-alzheimers-paper-potentially-misled-research/


Glenza, J. (2022, July 23). Critical elements of leading alzheimer’s study possibly fraudulent. The Guardian. https://www.theguardian.com/society/2022/jul/23/alzheimers-study-fraudulent


Kahler, L. (2015). Flickr. photograph. https://www.flickr.com/photos/64476765@N08/22105812861/in/photolist-zFq51v-9AMyPD-61eaPC-azgyor-azfm3R-azgwGn-J2aTFs-7kZX4P-azhHM7-azfs2B-sq4RNt-azf33B-azeYWg-azhzB5-azfx4v-azipeq-azhBMU-azgwRF-azeWhe-azia2s-azhH79-azgwxM-azf55T-azfeu8-azfSnK-Gd6RP7-azhEBq-azgycX-azf6qn-azjcjb-azi7q1-azixWW-7QGz6i-azfBN2-azfaWR-azhxgL-2mAJDgM-azga62-aziomq-azhBTA-azifU5-azhZis-dx5cff-e3y8nB-65GcEK-4eT3kD-7KXJ5b-azeZkT-azhzrh-azhEFq.


Li, X., Feng, X., Sun, X., Hou, N., Han, F., & Liu, Y. (2022, September 2). Global, regional, and national burden of alzheimer’s disease and other Dementias, 1990–2019. Frontiers. https://www.frontiersin.org/articles/10.3389/fnagi.2022.937486/full#:~:text=The%20countries%20with%20the%20highest,Table%203%2C%20Figure%203C


Lowe, D. (2022). Faked beta-amyloid data. what does it mean? . Science. https://www.science.org/content/blog-post/faked-beta-amyloid-data-what-does-it-mean


Lucchesi, E. L. B. (2022, October 14). “false” alzheimer’s study could set research back 16 years. Discover Magazine. https://www.discovermagazine.com/the-sciences/false-alzheimers-study-could-set-research-back-16-years


MacMillan, C. (2023, January 19). Lecanemab, the new alzheimer’s treatment: 3 things to know. Yale Medicine. https://www.yalemedicine.org/news/lecanemab-leqembi-new-alzheimers-drug#:~:text=The%20Food%20and%20Drug%20Administration,stage%20cases%20of%20the%20disease


Mamo, J. (2022, December 21). What allegations of alzheimer’s research fraud mean for patients. The Conversation. https://theconversation.com/what-allegations-of-alzheimers-research-fraud-mean-for-patients-187911


Pelc, C. (2022). Alzheimer’s study controversy: Where do we go from here? Medical News Today. https://www.medicalnewstoday.com/articles/alzheimers-study-controversy-what-does-it-mean-for-future-research#What-might-this-mean-for-dementia-research


Piller, C. (2022). Blots on a Field?. Science. https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease


Qiu, C., Kivipelto, M., & von Strauss, E. (2009). Epidemiology of alzheimer’s disease: Occurrence, determinants, and strategies toward intervention. Dialogues in clinical neuroscience. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181909/#:~:text=Prevalence%20of%20Alzheimer’s%20disease&text=Worldwide%2C%20the%20global%20prevalence%20of,and%206.4%20%25%20in%20North%20America


Rizzi, L., Rosset, I., & Roriz-Cruz, M. (2014). Global Epidemiology of Dementia: Alzheimer’s and vascular types. BioMed research international. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4095986/


Wong, W. (2020). Economic burden of alzheimer disease and managed care considerations. The American journal of managed care. https://pubmed.ncbi.nlm.nih.gov/32840331/


World Health Organization. (2022). Ageing and health. World Health Organization. https://www.who.int/news-room/fact-sheets/detail/ageing-and-health#:~:text=At%20this%20time%20the%20share,2050%20to%20reach%20426%20million



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