Book Review of C. Piller (2025). Doctored. Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s, Atria, One Signal Publishers, New York, Amsterdam, London, 352 pp.

Dr. G.J. van Bussel

Charles Piller is an investigative journalist renowned for exposing scientific misconduct, fraud, and ethical violations in biomedical research and public health. Writing for publications like Science, STAT News, and the Los Angeles Times, he examines how financial incentives, and institutional pressures compromise scientific integrity, covering topics from the reproducibility crisis to genetic engineering ethics and whistleblower challenges. Through meticulous document analysis, insider interviews, and critical scrutiny, Piller reveals the complex interplay between science, policy, and corporate influence, advocating for transparency and accountability while highlighting how systemic failures undermine public trust in scientific institutions. Piller’s investigations have triggered significant debate, paper retractions, and underscored journalism’s crucial role in safeguarding scientific integrity. From 2022 to 2024, he focused extensively on neuroscience fraud, particularly in Alzheimer’s research, publishing groundbreaking articles in Science that exposed data and image manipulation in clinical trials and revealed how Cassava Biosciences and researcher Hou-Yan Wang had manipulated data regarding the Alzheimer’s drug simufilam. [i] His February 2025 book Doctored. Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer’s synthesizes these individual cases into a comprehensive critique of the global Alzheimer’s research ecosystem, exposing how institutional policies, scientific misconduct, and distorted priorities have undermined the quest for effective treatments while leaving patients vulnerable to ineffective or dangerous experimental therapies.

In the Introduction, Piller articulates his central thesis: the dominance of the amyloid cascade hypothesis (the theory that Alzheimer’s disease stems from amyloid plaque accumulation) has stifled alternative research while fostering hype, wasted funding, and questionable breakthroughs. He is not the first to do so. [ii] Using Leqembi (a drug introduced in late 2022 that promised to be the long-awaited Alzheimer’s breakthrough) as his prime example [iii], Piller argues: “It was the latest example of the exaggeration, hype, and sheer fakery and fraud that has characterized Alzheimer’s research for decades. … I had to show why billions of dollars in spending by governments, pharma companies, and philanthropies had done little for desperate patients. For decades, proponents of the dominant amyloid hypothesis have sidelined, starved for resources, and even bullied rebels behind other promising notions of how to treat Alzheimer’s … Alzheimer’s research has offered endless opportunities for advancement and riches to corporate shysters and ruthlessly ambitious scientists who cut corners or engage in brazen deception. I set out to unmask decades of arrogance, greed, fabulism, and error that have emptied research coffers and littered the drug development landscape with failure after failure.” (pp. x-xi.) This narrative summary, while effectively encapsulating his book’s scope, opens him to criticism that the work could have been much shorter.

The twenty-two chapters that follow this introduction provide an in-depth elaboration of his argument, focusing on scientific misconduct, institutional failures, editorial policies, and commercial interests. These chapters are divided by me into five parts: Setting the Stage (chapters 1-5), A Rising Market (chapters 6-9), The Amyloid Mafia (chapters 10-13), Accountability Failures (chapters 14-17), and Meltdown and Hope (chapters 18-22).

The opening section, Setting the Stage, uses Stephen Price’s story — an Alzheimer’s patient enrolled in Cassava Biosciences’ simufilam trial — to illustrate the human cost of research misconduct, as his son Matt, an epidemiologist, grew concerned when ethical and legal requirements were compromised and the company failed to provide transparency regarding Stephen’s data. Subsequent chapters analyse what Piller calls the “hype, fakery and fraud that has characterised Alzheimer’s research for decades” (pp. x–xi), profiling simufilam’s architects Lindsay Burns, a brilliant neuropsychologist, and Hou-Yan Wang, a professor at the City University of New York, whose prestigious partnerships secured billions in market valuation, contrasted with neuroscientist and physician Matthew Schrag’s discovery of manipulated images in the drug’s foundational studies. Despite acknowledging that “disproving someone else’s experiment can be career suicide in science,” Schrag pursued his investigation because “a drug seemingly based on misconduct was taken by hundreds of unsuspecting Alzheimer’s patients” (both quotes on p. 38). The narrative also examines Sylvain Lesné and Karen Ashe’s 2006 Nature publication identifying Aβ*56 as proof of the amyloid hypothesis. The paper became a cornerstone of Alzheimer’s research with 2,500 citations. As Piller later demonstrates, the study was built on fragile, doctored, even fraudulent foundations.

The book’s second section, A Rising Market, chronicles the fraught commercialization of amyloid research through two parallel case studies: Biogen’s aducanumab (Aduhelm) and Cassava Biosciences’ simufilam. Despite nearly unanimous opposition from the US Food and Drug Administration’s (FDA) own advisory panel citing weak evidence and significant risks, Aduhelm was approved under an accelerated pathway requiring only amyloid reduction as a surrogate biomarker rather than proven clinical benefit, promoted by prominent amyloid advocates who were simultaneously highly paid Biogen consultants. The drug’s failure was sealed when a patient death was linked to treatment risks, while Cassava’s simufilam collapsed after Matthew Schrag exposed manipulated data in high-profile journals and clinical trial irregularities sparked legal battles. Through these twin narratives, Piller exposes a pervasive ‘revolving door’ between industry, academia, and the FDA, documenting how medical reviewers move directly from regulatory approval roles to lucrative positions at the companies they previously helped, while former FDA commissioners and leading academics join biopharmaceutical boards. This systemic enmeshment, Piller argues, created a culture prioritizing theory and profit over therapeutic truth and patient safety, enabling corporations to profit from marginally effective therapies while avoiding meaningful accountability. [iv]

The third section, The Amyloid Mafia, investigates two interwoven narratives: Michael Schrag’s discovery of significant image irregularities in Lesné and Ashe’s highly cited 2006 publication, validated with help from specialists like Elisabeth Bik, and Piller’s exposure of a powerful network of researchers, journal editors, and biopharma stakeholders who have tenaciously perpetuated the amyloid hypothesis despite its limited therapeutic success. This informal ‘Amyloid Mafia’ effectively controls scientific enterprise by influencing major grants, publication access, and career advancement while systematically marginalizing alternative theories, leveraging their entrenched influence within FDA advisory panels, lucrative consultancy roles, and dominance of peer-review processes for considerable personal benefit. Piller’s interviews with the ‘victims’ of this system — often highly cited scientists marginalized for challenging the orthodoxy — prove particularly illuminating, while Schrag’s evidence of data manipulation extends beyond the Lesné-Ashe paper to numerous other publications within the network. The fallout has included paper retractions, delayed journal responses, lengthy institutional investigations, and a widespread culture of lax accountability for scientific misconduct, demonstrating how this network’s influence required incontrovertible evidence to challenge.

The fourth section, Accountability Failures, examines how institutional and ethical environments enabled persistent misconduct and produced deficient responses to its disclosure. Federal agencies consistently disregarded allegations and evidence, as was exemplified when Dr. Schrag was removed from an NIH grant application after identifying image manipulation, yet the grant was still awarded to the implicated team. Mirroring the failings of the FDA, the NIH neglected to intervene and dismissed whistle-blower concerns, thereby perpetuating the dominance of the amyloid-beta hypothesis despite confronting evidence that challenged its validity. Academia propagated deceit through data misrepresentation by reputable scholars, subverted peer review, and journals’ pronounced reluctance to issue corrections. Publishers employ dilatory tactics to suppress criticism and enacting sluggish retractions only when allegations became incontrovertible and public. Journal editors permitted citation of retracted papers, perpetuating spurious scholarship. Piller argues these deceptive practices are systemic, arising from universities competing for prestige and grant income, senior academics invested in specific hypotheses, and institutional failure to discipline challenged faculty. Even a close associate of Dr. Schrag’s took considerable liberties in presenting research.

The final section, Meltdown and Hope, examines the cascade of fraudulent publications exposed following the Ashe-Lesné scandal, implicating dozens of neuroscientists — including several of the world’s most prominent researchers like Eliezer Masliah, Berislav Zlokovic, and Adriano Aguzzi — for using manipulated imagery in their studies. While Professor Ashe accepts personal responsibility, she continues defending the 2006 paper’s fundamental conclusions, even if the results cannot be replicated consistently. The continued citation of these doctored papers has rendered vast amounts of research problematic, creating a years-long process of discerning reliable research from compromised work. Matthew Schrag concludes that the principal lesson from uncovering this scientific misconduct is the imperative to “very intentionally teach research ethics and integrity when we’re training students so that it becomes ingrained in our identity as scientists” (p. 261), offering a path forward through fundamental reform of scientific training and ethical education. Piller outlines potential reforms, advocating for greater transparency in research, stricter regulatory oversight, and diversification of funding beyond amyloid-centric studies. While these proposals are sound, they lack concrete policy mechanisms, leaving questions about feasibility unanswered.

Piller is not the first to report on scientific misconduct and fraud, but he is among the first to demonstrate that such misconduct may be endemic and systemic rather than merely the product of individual arrogance and ambition. This conclusion gains support from recent research indicating that fabrication and falsification of results may be more prevalent than previously recognized, with one review estimating that approximately one in seven papers are fake (14-15%), a figure likely much higher when including questionable research practices. [v] It’s not a problem confined to Alzheimer’s research alone. As of September 2025, at least 60,000 scholarly studies have been retracted, according to the Retraction Watch database from the Centre of Scientific Integrity. An estimated several hundred thousand fraudulent studies remain in circulation unidentified. [vi] The integrity of the scientific record is being undermined through shortcomings in the systems through which scientists infer the trustworthiness of each other’s work. [vii]

Piller’s most significant achievement lies in his masterful synthesis of investigative rigour and compelling narrative. By drawing on insider testimony and leaked documents, he builds a solid foundation of evidence for his claims while maintaining a narrative that engages the reader. His examination of systemic institutional failures makes a compelling case for comprehensive reform within the research establishment. However, the book’s impact is somewhat diminished by Piller’s reluctance to engage substantively with opposing perspectives. A more balanced consideration of scientists who acknowledge the profound flaws in amyloid research yet argue for its scientific value would have strengthened Piller’s central thesis rather than weakened it. While the author does not explicitly deny that the hypothesis may yet hold some merit, this concession could have been articulated more effectively. Furthermore, while the focus on American regulatory failures is warranted, incorporating perspectives from international research environments would have considerably enhanced the work’s applicability and relevance on a global scale.

Piller offers a scathing critique of several fundamental issues within modern academia, including the pervasive ‘publish or perish’ culture, immense financial pressures favouring positive results, the fragility of the peer-review system, the challenges faced by whistleblowers, and the conflicts of interest that arise when academic research is closely linked to commercial ventures. In its endeavour to present a compelling narrative, some critics emphasize, the work occasionally oversimplifies the inherently complex and messy nature of scientific discovery. However, true as this may be, this does not excuse the manipulation of data and the alteration of images. Widespread misconduct has been proven and cannot be ignored. But, as one of the reviewers of the book explicitly states: “I contacted some Alzheimer researchers who know me to ask if they would write a short critique of the Piller arguments, based on his articles that are much shorter than the book, without needing to read the book. Two failed to respond and the third called me to explain that he wouldn’t do it, as the Alzheimer research community had decided (I did not ask how this happened) to never engage with the author. I was gobsmacked.” [viii] Admitting that an unproven hypothesis is not the breakthrough it was promised to be proves very difficult, even when misconduct and fraud are foundational for its popularity.

Doctored is not a neutral report. Rather, it is a compelling argument based on thorough research. Despite its repetitiveness and the inclusion of a lot of irrelevant information, it is a book that demands to be read. Ultimately, it is both essential and provocative, exposing alarming truths about Alzheimer’s research, albeit occasionally sacrificing nuance for rhetorical impact (‘Amyloid Mafia’). The book is a call for greater accountability, arguing that the quest for a cure should be driven by patients’ interests rather than profit.

This highly recommended book is an essential text for all members of the academic and scientific research community. It shines a spotlight on the systemic pressures and perverse incentives that can compromise scientific integrity. Piller’s investigative work compels every reader to confront two profoundly uncomfortable yet vital questions: can we truly guarantee that our own research environments are immune to the forms of misconduct and ethical failure so starkly detailed within these pages? More importantly, if such a guarantee cannot be made — as the book persuasively argues — what concrete, collective actions must we undertake to foster a culture of robust transparency, rigorous accountability and unwavering ethical commitment? This book is not just a diagnosis of a problem; it is a catalyst for the urgent dialogue and reform that are needed.

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[i] C. Piller (2022). ‘Research backing experimental Alzheimer’s drug was first target of suspicion’, Science, Vol. 377, No. 6604, p. 363; C. Piller (2022). ‘Blots on a field?’, Science, Vol. 377, No. 6604, pp. 358-363; J. Couzin-Frankel, and C. Piller (2022). ‘Alzheimer’s drug stirs excitement-and concerns’, Science, Vol. 378, No 6624, pp. 1030-1031; C. Piller (2023). ‘Report on trial death stokes Alzheimer’s drug fears’, Science, Vol. 380, No. 6641, pp. 122-123; C. Piller (2023). ‘Probe of Alzheimer’s studies finds ‘egregious misconduct’, Science, Vol. 382, No. 6668, pp. 251-252; C. Piller (2023). ‘Brain games?’, Science, Vol. 382, No. 6672, pp. 754-759; C. Piller (2024). ‘‘Damning’ FDA inspection report undermines Alzheimer’s drug’, Science, Vol. 383, No. 6688, pp. 1165-1166; C. Piller (2024). ‘Authors move to retract discredited Alzheimer’s study’, Science, Vol. 384, No. 6700, p. 1055; C. Piller (2024). ‘Challenged papers underpin several drugs’, Science, Vol. 385, No. 6716, p. 1410; C. Piller (2024). ‘Picture imperfect’, Science, Vol. 385, No. 6716, pp. 1406-1412; C. Piller (2024). ‘Firm misled investors on Alzheimer’s drug. SEC charges’, Science, Vol. 386, No. 6717, p. 15.

[ii] K. Herrup (2015). ‘The case for rejecting the amyloid cascade hypothesis’, Nature Neuroscience, Vol. 18, No. 6, pp. 794-799 and G.P. Morris, I.A. Clark, and B. Vissel (2018). ‘Questions concerning the role of amyloid-β in the definition, aetiology and diagnosis of Alzheimer’s disease’, Acta Neuropathologica, Vol. 136, No. 5, pp. 663-689.

[iii] See also: M. Kurkinen (2023). ‘Lecanemab (Leqembi) is not the right drug for patients with Alzheimer’s disease’, Advances in Clinical and Experimental Medicine, Vol. 32, No. 9, pp. 943-947.

[iv] See also: A. Lundh, J. Lexchin, B. Mintzes, J.B. Schroll, and L. Bero (2017). ‘Industry sponsorship and research outcome’, Cochrane Database of Systematic Reviews, Vol. 17, No. 2. Art. No.: MR000033. Online source, retrieved September 10, 2025, from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.MR000033.pub3/full.

[v] ‘How many scientific papers are fake?’. Blog. ME/CFS Science. A critical view into ME/CFS research, March 17, 2025. Online source, retrieved on September 10, 2025, from: https://mecfsscience.org/how-many-scientific-papers-are-fake/. Partly based on: J. Heathers (2024). How much science is fake? Approximately 1 in 7 scientific papers are fake’. Online source, retrieved on September 10, 2024, from: https://osf.io/s4gce. On p. 18 of his research paper, Heathers states: “Likewise, if this is the rate of fake papers, then the presumably higher number of papers containing questionable research practices (which are far more commonly admitted to) is presumably higher still.”

[vi] E. Spitznagel (2025). ‘How greed and profit fueled one failed Alzheimer drug’, The New York Post, February 9. Online source, retrieved September 10, 2025, from: https://nypost.com/2025/02/09/lifestyle/how-greed-and-profit-fueled-one-failed-alzheimer-drug/. In February 2025, 55,000 retractions were mentioned on Retraction Watch.

[vii] R.A. Richardson, S.S. Hong, J.A. Byrne, T. Stoeger, and L.A.N. Amaral (2025). ‘The entities enabling scientific fraud at scale are large, resilient, and growing rapidly’, Proceedings of the National Academy of Sciences, Vol. 122, No. 32, e2420092122, recognizes the same systemic problems Piller does.

[viii] J.H. Friedman (2025). ‘Book review: Doctored: Fraud, Arrogance and Tragedy in the Quest to Cure Alzheimer’s, Rhode Island Medical Journal, Vol. 108, No. 3, pp. 51-52. For quotation: p. 52.