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Decoding Darkness: The Search For The Genetic Causes Of Alzheimer's Disease

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Decoding Darkness takes you on a fascinating and humorous journey into the world of research. Rudolph Tanzi and Ann Parson have put together an interesting and entertaining book on a very serious subject, Alzheimer's Disease. The book takes you from Tanzi's graduation from University of Rochester to his graduation with a PHD in neurogenetics from Harvard University, to the early days of his research to the present. Decoding Darkness is a must read for anyone's family who has been afflicted with this horrible disease to anyone who is interested in the fascinating world of research and the "heroes" such as Rudolph Tanzi who dedicate their lives to cure these deadly diseases.

This is an excellent book on Alzheimer's research. It covers almost all aspects of interest in the field including genetics, molecular biology, drug discovery and clinical characteristics. The history of the various different discoveries is compellingly narrated and full of little anecdotes and sidelines, which makes the subject so much more fascinating and brings you very close to the people actively (and passionately) involved in all major advancements. In addition, the authors took great care to explain the complex biological processes and interactions of Alzheimer's disease using everyday English, avoiding scientific terminology whenever possible. This makes the book a highly enjoyable read not only for scientists and clinicians, but also - and especially - for the interested lay audience. It's a prime example that science writing does not have to be dry, dull and incomprehensible, but can be as exciting as reading a detective story: once you've started you just want to learn more and more and cannot stop until you have reached the last page. I can highly recommend 'Decoding Darkness' for everyone who is interested in how scientists from all over the world have been engaged in solving the many mysteries and riddles that lie behind this devastating disease.

"Decoding Darkness" by Rudolph E. Tanzi, Ph.D. and science writer,. Ann B. Parson, is a very thought-provoking book. Tanzi is the Director of the Genetics and Aging Research Unit of the Harvard University Medical School. This book reads like a detective story of the author's view of the neurogenetic research leading up to a possibly effective vaccine that we hope will prevent and even may cure Alzheimer's Disease [AD].

To set the stage for the timeliness of the book, I report that the World Alzheimer Congress 2000, of July 9-18 was held in Washington, DC. In a plenary session Dr. Dale Schenk presented a pivotal paper on Elan Pharmaceuticals' new vaccine. He stated that the vaccine is " a disease-modifying therapy that appears in reach. Indeed A-beta modulation may enable physicians, patients, and caregivers to look to the future with optimism and hope".

In the preface we learn that Tanzi is a founder of Prana Biotechnology, Genoplex and Neurogenetics. He has equity in Elan Pharmaceuticals and Bristol-Myers-Squibb.

It is hoped that the Elan vaccine will decrease beta-amyloid production in the brain by blocking gamma secretase, an enzyme that separates beta-amyloid from a larger protein and releases it into the brain. So far Elan has completed the FDA Phase I drug trial for safety. There is no way to predict how the Phase II trial for efficacy will work clinically on humans. It had been tested on transgenic mice.

Dr.Tanzi's style of writing presupposes that the reader has been schooled in the field of neurogenetics.To help the layperson, it is imperative to develop a glossary of at least 100 or more terms. Phrases such as cholinesterase inhibitor, beta-amyloid and gamma secretase, etc. must be understood to better appreciate this book. Therefore I am providing a minimal glossary, at least of those terms found in this book review for laypersons . Please see below.

Throughout the book, credit is given to George Glenner, a scientist who spent many years at the National Institute of Health [NIH] and since 1980 has been at UCSD [La Jolla,Ca.]. On May 16, 1984, Drs. Glenner and Cai'ne Wong published a paper on their breakthrough in isolating brain amyloid beta peptide. I believe that since their first meeting in 1988, Glenner had a profound influence in Tanzi's career.

Dr.Tanzi gives us an insight into the seminal work of Dr.Dmitry Goldgaber, formerly of N.I.H. Dr.Goldgaber had been on the staff of Nobel Laureate Charlton Gajdusek. He now is a Professor of Psychiatry at SUNY-Stony Brook Medical School and is Chair of the LIAF Scientific Advisory Board. Tanzi writes of Goldgaber that "His team had isolated a portion of Alzheimer's amyloid, it was on chromosome 21, and here was the DNA sequence as proof." He reported this at the 16th annual meeting of the Society for Neuroscience in November 1986. He described the APP gene. "APP" stands for Amyloid Precursor Protein. It is the precursor of the amyloid protein that is deposited in the AD brain. Tanzi attended this meeting. In the February, 1987 issue of SCIENCE, Tanzi and Harvard colleagues wrote a paper describing the isolation of the amyloid gene. This was a very exciting time!

The author credits Dr. Peter Davies of the Albert Einstein School of Medicine as having "clinched the cholinergic evidence". Davies also provided the lasting value of revealing that tangles were only "the tip of the iceberg of a very widespread tau-related abnormality" that begins far earlier in the disease process. He still believes in this theory. I had wished that the book had made a detailed comparison of the tau versus the amyloid theory.

The book in several chapters refers to the work of Dr. Peter St.George-Hyslop, now at the University of Toronto and his research on a major early onset AD mutant gene in chromosome 14. In 1995

Aricept [Pfizer] an FDA appoved cholinesterase inhibitor, is only briefly mentioned in the book. There are about three years of studies by Pfizer showing the efficacy of this drug in delaying the symptoms of Alzheimer's Disease [AD]. The author does not mention most of the new medicines in the AD research "pipeline", such as Reminyl [ Phase III], Memantine [ Phase III at NYU Medical Center] and Cerebrolysin [Phase III in Canada] Also not referred to is Neotrofin [Neotherapeutics], a neotrophic growth factor medicine [ Phase II b]. Many of these show promise for AD help and may receive FDA approval in the next year or two, or sooner.

The anti-amyloid-beta drugs discussed in the author's last chapter claim to hold much promise for AD patients, but they may be many years away from FDA approval.

"Decoding Darkness" is a highly technical book that imparts much information on an aspect of Alzheimer's Disease, and with some serious study of terminology is an engrossing publication. Dr.Tanzi's book has an excellent index, which among other items provides the names of over 165 notable researchers in the field of AD. One can obtain MEDLINE abstracts of many of these scholars' works by accessing PubMed at URL<http://www.ncbi.nlm.gov/PubMed. This book requires intense concentration to comprehend. However, the information gleaned from it is well worth the effort. REVIEWER'S GLOSSARY

[1] Beta- amyloid is a protein derived from a larger precursor protein and is a component of brain tangles and plaques characteristic of AD. [2] Cholinesterase is an enzyme that breaks down a neurotransmitter vital to proper brain functioning. [3] Chromosome is one of the usual elongated bodies in a cell nucleus that contains most or all of the DNA comprising the genes. [4] Beta-secretase and gamma-secretase are two proteases [enzymes which hydrolyze proteins] that cleave amyloid protein, producing amyloid peptide. [5] Modulation means to regulate or modify a natural process in the body. [6] Neurogenetics is a branch of genetics dealing with the nervous system and its development. [7] Neurotrophic factors: [A] Nerve Growth Factor [NGF] is essential to the development and maintenance of peripheral as well as central neurons. [B] Neutrophin-3 stimulates nerve growth in different populations of neurons than NGF. [C] Fibroblast Growth Factor, basic [bFGF] is important for the initiation of nerve repair after injury and promotes proliferation of immature neurons. bFGF is the neotrophic factor that causes multiplication of neurons. [8] tau protein may have been found by staining brain tangles with antibodies. Researchers have doggedly stuck with this lesion and are realizing that the tangle sub-unit resembled a modified form of a protein called tau . [9] Transgenic mice are mice whose genomes are manipulated in such a way that they either have an extra copy of a gene or one of theirs is removed. These mice are widely used now in biomedical research, including that in Alzheimer's Disease.

Decoding Darkness provides not only the scientific facts about what is known about Alzheimer's disease, but also the historical aspects behind it. This book is a very interesting book to read. I thought it would be another textbook-like format explaining about Alzheimer's disease, but it was more like a detective novel developing into the current state of Alzheimer's disease research in reality. This book was written by one of the very first in the frontiers of Alzheimer's disease research. The information should be accurate and most current.

Decoding Darkness is a fascinating book that takes into the world of research. After reading this book, you will no longer think of scientist as nerdy little men and women in white coats, but as real people who dedicate their lives to save others. The book reads easily, as it is interesting, informative, and written humerously.

Tanzi and Parsons have written the best science-hunt book since The Double Helix. Tanzi's adult life has clearly been dedicated to the search for the causes of Alzheimer's disease, and his single-minded drive comes through in every page. It is fascinating to learn how passion rules not just art and performance professions, but also (perhaps even to a greater degree) scientific research. The fun, excitement and committment of Tanzi and his colleagues in their pursuit of this disease is related with candor and vividness, and is truly accessible to the lay audience. Tanzi and Parsons have successfully spanned both art (music), philosophy (taoism) and science (genetics) with admirable elan. The book has its biases, but the authors do not hide the autobiographical nature of the narrative. Science might also be written by the victors, and Tanzi and his brilliant team of scientists deserve to record their history, since their contributions have changed the world we live in. The book ends with a vision that this previously hopeless disease will be conquered within our lifetimes. This is a fascinating, and exhilirating perpective. I recommend this book to all science readers with great enthusiasm.

Tanzi and Parson tell a fascinating story of medical discovery with great excitement and clarity. The science was not sugar coated, but was very clearly explained and written in a very literary and often amusing manner. The descriptions of the human genome project in this book were in many ways superior to those that have appeared in books prepared specifically on the topic. My interest in this book was prompted not so much from an interest in Alzheimers disease but originally came from a recommendation from a friend who actively reads books about the human genome revolution and gene research. After reading the book, I would definitely agree with her opinion that no other book in the genre explains the goals behind the human genome project (and especially how they relate to disease based research) as well as "Decoding Darkness". Also, the story of the family with inherited Alzheimers that runs parallel with the main story about the research was quite touching and provided a very nice break the excitement and hustle and bustle of the research discoveries described. Overall, I would have to say this is one of the best science genre books I have ever read...maybe the best after "The Double Helix". HIGHLY RECOMMENDED!!!

This book provides a rare opportunity. It allows a glance into the dynamic world of the scientists responsible for our understanding of Alzheimer's disease. The unique perspective and fair editorializing of Rudy Tanzi, a scientist long at the frontier of neurogenetics, makes the book more engaging and humanistic. Parts of it, though factual accounts, are so exciting they read like part of a fanciful novel. The explanations of the science of Alzheimer's disease should be accessible to any reader and may provide historical insight to those immersed in the field. Read this book!

I found this book to be extremely intersting. In it Dr. Tanzi follows both his career and the evolution of our knowledge concerning Alzheimer's Disease. He vividly describes the thrills and disappointments that come with research, all set within the context of trying to figure out what is the cause and some possible treatments of Alzheimer's. Tanzi guides the reader through the technical aspects of what is known about the disease and what has yet to be discovered. I think that most people would enjoy it, although the reader must be aware that there are some more technical aspects to his discussion.

Decoding Darkness charts the search for the genetic causes of Alzheimer's disease, detailing the studies which have taken place and the promising theory which could help promote new drugs in the battle against Alzheimer's. Lay readers and medical personnel alike will find this a fascinating medical detective treatise which probes molecular clues to illness and therapeutic applications.