- Paperback: 304 pages
- Publisher: Basic Books; 1 edition (December 2001)
- Language: English
- ISBN-10: 0738205265
- ISBN-13: 978-0738205267
- Product Dimensions: 6.1 x 0.8 x 9.2 inches
- Shipping Weight: 13.4 ounces (View shipping rates and policies)
- Average Customer Review: 12 customer reviews
- Amazon Best Sellers Rank: #716,252 in Books (See Top 100 in Books)
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Decoding Darkness: The Search For The Genetic Causes Of Alzheimer's Disease 1st Edition
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Alzheimer's disease, a fatal, annihilating brain disorder, affects millions of men and women around the world. In the United States alone, perhaps one in five persons aged 75 or older suffers from it, though hundreds of thousands of younger people also bear the condition.
Despite its ubiquity, the malady was, until recently, considered a "backwater disease" to which little research attention (and funding) was paid. Advances in gene research, some spearheaded by neurologist Rudolph Tanzi, have led to a new understanding of the causes of Alzheimer's disease, and new possibilities for its cure. In this well-written account of that research, Tanzi and journalist-co-author Ann Parson examine the role of amyloid neuritic plaque, "mucked-up, misfolded protein that fibrilizes and forms rock-hard aggregates that the body can't get rid of." This plaque occurs in humans and certain other carnivorous species (including bears and dogs), and it appears to play a role in neurologic disorders of several kinds. Tanzi reports on recent studies in the use of cholesterol-reducing drugs in lessening levels of "brain dirt," as well as on research that suggests that cardiovascular exercise and a diet low in animal fats can benefit the brain as well as the body. He even cautiously hints that the conquest of Alzheimer's may occur in the very near future. For the time being, his book provides a thoughtful portrait of the illness and of the scholars and scientists who have devoted their lives to combating it. --Gregory McNamee --This text refers to an out of print or unavailable edition of this title.
From Publishers Weekly
At the turn of the 21st century, Alzheimer's is the fourth leading cause of death of Americans. Twenty years ago, Tanzi, now a professor of neurology at Harvard Medical School and director of Massachusetts General Hospital's Genetics and Aging Unit, worked in a study examining the genetics of Huntington's disease, and while doing so he developed a method for locating disease genes and their proteins., Starting in the 1980s Tanzi applied these methods to the search for the cause or causes of Alzheimer's, a neurogenerative disease similar to Huntington's. In this fascinating storyDpart mystery, part scientific treatise, and part autobiographyDTanzi recounts every step along the way of the search. His own research rests on the hypothesis that deposits of the gummy protein amyloid form millions of plaques that settle between brain cells in the cerebral cortex as the result of a genetic mutation, and he chronicles the search for the gene that contains this mutation. Tanzi's tale (told with the help of science journalist Parson) is not just another sterile account of scientific discovery, as he weaves into his narrative the poignant stories of Alzheimer's families with whom he has worked and patiently guides readers through his own process of discovery and its implications for the future of Alzheimer's patients. (Nov.)
Copyright 2000 Reed Business Information, Inc. --This text refers to an out of print or unavailable edition of this title.
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-Jacqueline Marcell, Author 'Elder Rage, or Take My Father... Please! How to Survive Caring for Aging Parents', International Speaker on Eldercare & Alzheimer's
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<[...] This book requires intense concentration to comprehend. However, the information gleaned from it is well worth the effort. REVIEWER'S GLOSSARY
 Beta- amyloid is a protein derived from a larger precursor protein and is a component of brain tangles and plaques characteristic of AD.  Cholinesterase is an enzyme that breaks down a neurotransmitter vital to proper brain functioning.  Chromosome is one of the usual elongated bodies in a cell nucleus that contains most or all of the DNA comprising the genes.  Beta-secretase and gamma-secretase are two proteases [enzymes which hydrolyze proteins] that cleave amyloid protein, producing amyloid peptide.  Modulation means to regulate or modify a natural process in the body.  Neurogenetics is a branch of genetics dealing with the nervous system and its development.  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.  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 .  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.