Edited by Dennis J. Selkoe, Eckhard Mandelkow, and David M. Holtzman 511 pp, $135 Cold Spring Harbor, NY, Cold Spring Harbor Laboratory Press, 2011 ISBN-13: 978-1-936113-44-6 The study of Alzheimer disease has undergone rapid change in recent years. Research has revealed exciting advances in the understanding of the biology of the disease and its clinical course. The recent revision of Alzheimer diagnostic criteria represents an important milestone resulting from the integration of decades of work conducted among animals and humans on the biological markers of disease. However, these developments have also been accompanied by frustrating challenges in drug trials and prevention, because there still is no successful preventive or disease-modifying treatment. The fast-paced nature of Alzheimer research thus generates a moving target for researchers, medical professionals, and the interested public who seek to stay up to date with the field. The publication of The Biology of Alzheimer Disease, part of the Cold Spring Harbor Perspectives in Medicine series, addresses this need by providing a comprehensive summary of basic and applied research on the molecular biology, neurochemistry, and genetic basis of Alzheimer disease. The book was an ambitious project, given the challenge of covering the breadth of work and its controversies in a way that will withstand the test of time. But editors Dennis Selkoe, Eckhard Mandelkow, and David Holtzman, who are responsible for some of the most influential work in the field, have succeeded in assembling the definitive volume on the biological basis of Alzheimer disease. The topics covered range from epidemiology to biochemistry, and chapters are written by top experts in each area. As the title suggests, the core chapters focus on biological mechanisms underlying the disease, including amyloid and tau protein aggregation and clearance, presenilin, amyloid precursor protein, inflammation, ubiquitin, apolipoprotein E, and animal models. A unique feature that differentiates the book from review articles is that the authors frequently emphasize the historical context and scientific relevance of these mechanisms in an interesting and readable way. For example, one chapter describes decades of work uncovering the many complex forms of the β-amyloid protein, from soluble oligomers to insoluble fibrils, making up the classic extracellular plaques seen at autopsy. Work with various amyloid assemblies in animals led to the surprising—and provocative—idea that soluble amyloid oligomers may play a greater neurotoxic role than amyloid in its more developed fibrillar forms. The book is of sufficient depth to be a valuable resource for established scientists seeking to expand their knowledge beyond their specific area of expertise, but the breadth of the topics covered and the clear and comprehensible writing style will also make the book widely accessible for the academic research community, graduate and medical students, and clinical practitioners with an interest in biological mechanisms. In addition to the sections focusing on core biology, the emphasis on history, relevance, key unresolved questions, and future predictions will make the work accessible to people with a variety of backgrounds. The book is also accessible on a practical level: the 23 sections are each available for download on the Cold Spring Harbor Perspectives in Medicine website. The entire collection is searchable on the website as well. Clinical, neuropsychological, and epidemiologic perspectives are also covered, along with recent important developments in neuroimaging and other biomarkers. There is some discussion about clinically relevant topics such as the new diagnostic criteria for Alzheimer disease, neurovascular dysfunction, neuropsychological and neuropathological differentiation of Alzheimer disease from other dementias, and the use of positron emission tomography, magnetic resonance imaging, and measurement of cerebrospinal fluid biomarker levels in the increasing emphasis on early detection and secondary prevention. Several chapters also focus on the history and current status of amyloid- and tau-directed and other therapies. However, patient diagnosis and management is not the focus of the book, so medical professionals seeking practical information on the use of biomarker measurements in the clinic should look elsewhere. Another unique challenge the editors faced was how to handle the long history of controversial ideas and differing opinions in Alzheimer research, given the large number of unanswered questions and conflicting findings. The most obvious controversy is the long-standing debate between “TAUists” and “BAPtists,” who respectively argue for the primary role of tau or the β-amyloid proteins in the initiation and proliferation of pathology. This debate has led to much discussion surrounding recent models integrating the temporal order series of pathological events, but the amyloid hypothesis has generally dominated within the scientific community, and an undercurrent of this view is evident throughout the book. It is certainly possible that this perspective may change in coming years, given the rapidly changing landscape in research and drug development. The book's diversity of expertise and integration of controversial ideas is also reflected in the editors' own areas of expertise. The editors contributed to chapters on the roles of amyloid (Selkoe), tau protein (Mandelkow), and the ApoE gene (Holtzman) in the development of disease. The editors and authors have addressed controversies in the field by including chapters on a broad range of topics coauthored by researchers who hold differing views or have published separately on the same topics. Several authors provided the much-needed insight that while existing models are helpful as heuristics, they are likely to be a simplification of the vast and complex set of physiological processes involved in the disease. The Biology of Alzheimer Disease, written by the top scientists in the field, fills a critical void by providing a thorough and up-to-date review of the biological mechanisms underlying the development of Alzheimer disease. Back to top Article Information Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Landau reported serving as a consultant for Avid Radiopharmaceuticals, receiving past consulting fees from Janssen Alzheimer Immunotherapy, and that he was employed by Avid Radiopharmaceuticals between December 2011 through March 2012 in addition to his principal employment at University of California, Berkeley. Dr Doraiswamy reported receiving consulting/speaking fees from Avid/Lilly, Accera, AstraZeneca, Bayer, Baxter, Bristol-Myers Squibb, TauRx, Neuroptix, Piramal, Avanir, and Sonexa; receiving grants or grants pending from Elan, Avid/Lilly, Novartis, Janssen, Pfizer/Medivation, the National Institutes of Health, the Alzheimer Drug Discovery Foundation, Neurometrix, the Northern California Research Institute, Lundbeck, and the Alzheimer's Association; receiving royalties from St Martin's Press; and that he owns stock in Sonexa and Clarimedix, whose products are not discussed in this review.
JAMA – American Medical Association
Published: Nov 14, 2012