Book Review: How Not to Study a Disease

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In today’s post, I’d like to draw your attention to an absolutely amazing book on the topic of Alzheimer’s disease. Written by Prof. Karl Herrup, professor of neurobiology at the University of Pittsburgh School of Medicine, “How Not to Study a Disease – The Story of Alzheimer’s” takes the reader on a journey of Alzheimer’s research from its inception by Alois Alzheimer to the contemporary understanding of this devastating condition.

This is not just another textbook account of the disease’s biology; instead, it offers a unique examination of the research that has shaped the field, highlighting the missteps along with the advancements. It dissects the progression of theories, reflecting on why certain hypotheses gained prominence, while others were left in the dust, and importantly, it provides pointers for future explorations in Alzheimer’s research.

Personally, I love the fact that this book puts into perspective why the amyloid hypothesis (i.e. the idea that an accumulation of amyloid beta plaques in the brain is the cause of Alzheimer’s) has dominated the field for so long, in spite of what can be considered objectively miserable failures, in spite of alternative hypotheses (for example, regarding the role of the immune system), as well as in spite of relatively compelling evidence that amyloid does not necessarily equal Alzheimer’s.

Prof. Herrup identifies three crucial moments that have contributed to the research into Alzheimer’s disease evolving as it has. The first occurred more than 100 years ago, when Alois Alzheimer’s boss, Emil Kraepelin, decided to include the two case studies Alzheimer had been studying into a textbook and to name them Alzheimer’s disease. The second and third happened more recently, and involved drawing equivalence between presenile dementia (i.e., a rare genetic disease that had been previously known as Alzheimer’s disease, but might be more familiar to you as familial Alzheimer’s) and senile dementia (i.e., old age cognitive decline), and expanding the definition of Alzheimer’s by including a preclinical stage (i.e., when amyloid plaques are already present, but symptoms aren’t there yet).

Nevertheless, the book ends on a positive note, highlighting the fact that, even though most research avenues didn’t receive as much attention as the amyloid hypothesis, we are not actually starting from scratch and there are a lot of viable alternative hypotheses to explore.

Importantly, Prof. Herrup is not an isolated voice calling for a re-evaluation of the amyloid-centric approach. In recent years, there has been a growing chorus of researchers advocating for a more diversified research agenda, inclusive of alternative hypotheses. This shift in thinking marks a promising evolution in the field, signaling a renewed openness to exploring different paths towards understanding and ultimately conquering Alzheimer’s disease.

To sum up, Prof. Herrup’s book serves as a vital reminder of the importance of scientific curiosity and open-mindedness. It calls on the scientific community to not be swayed by the allure of a single, dominant theory, but rather to embrace the multiplicity of ideas that can collectively bring us closer to solving the Alzheimer’s puzzle. This book is a must-read for anyone interested in the past, present, and future of Alzheimer’s research. It not only provides valuable insights into the complexities of the disease, but also sparks an important conversation on the need for a paradigm shift in the approach to finding a cure.

Further reading

Herrup, K. (2021). How not to study a disease: the story of Alzheimer’s. MIT Press.

Panza, F., Lozupone, M., Logroscino, G., & Imbimbo, B. P. (2019). A critical appraisal of amyloid-β-targeting therapies for Alzheimer disease. Nature Reviews Neurology15(2), 73-88.

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