Doctored is a fascinating, sobering read. The book, written by an investigative journalist, relates the discovery of an array of suspect images that have appeared in the pages of peer-reviewed research articles focused on the biological basis and potential pharmacotherapy for Alzheimer’s disease. The suspect images are mainly Western blots, used to identify specific proteins. Expert scholars and clever computers can spot signs of manipulation, such as sections added, that might indicate the presence of a protein that was not actually found, and duplication, such as re-using a previously published image in a later article. The revelations relate to a spectrum of researchers mainly, but not exclusively, in the USA, where the journalist is based, from those at the start of their careers through to established well-known senior figures, and mainly, but not exclusively, to the amyloid cascade hypothesis. Taken together, they raise serious questions about the validity of findings that have laid the foundations for huge investment to develop drugs in the hope that clearance of beta-amyloid plaques could slow or halt the progression of Alzheimer’s or even lead to improvement in the cognitive functioning of those living with the disease.

Anyone who works in the field of dementia knows of successive disappointments related to drug discoveries. Just 2 years ago, lecanemab and donanemab were licensed in the UK, with lecanemab described on the gov.uk website as ‘the first treatment for Alzheimer’s disease [. . .] that shows some evidence of efficacy in slowing progression of the disease’. Their approval led to a flurry of activity around how to accommodate the necessary administrations of regular infusions, only alleviated when the National Institute for Health and Care Excellence (NICE) decided they were not cost-effective enough to be offered on the NHS (though this decision is currently under review). Doctored provides a plausible explanation for the limited benefits of these drugs by exposing the interplay of pressures on researchers to publish, lack of will by senior researchers and institutions to act in the face of irregularities and a pharmacological industry racing to gain investment or reap profits. It is proposed that this combination has led to poor science underlying an unmerited focus on drugs to clear amyloid at the cost of exploring other avenues.

The writing took me, one step at a time, into a world about which I knew almost nothing. Charles Piller, the author, is at pains to show how carefully he has selected his sources. He relies heavily on a scientist, Matthew Schrag, who understands Western blots and who is portrayed throughout as highly ethical and reluctant to judge others. Piller’s tale starts with small beginnings of suspicion of fraud in one small US team, but the thread he pulls leads to more and more unravelling across an increasingly wide landscape. The work shows the place of greed and glory-seeking in the world of drug discovery. This is not an academic text but provides a thought-provoking read, reminding us that integrity in research is absolutely vital if we are to serve well those living with Alzheimer’s disease.