Table of Contents
Table of Figures
For the Noonans and all others confronted by this disease,
and for
Ann M. & Rudolph A. Tanzi, and
Katharine & Christopher Rodgers
Acknowledgments
The idea for this book occurred on Bostons Storrow Drive on November 7, 1995. That days horoscope in the Boston Globe seemed to indicate a go. Its advice: Eliminate the word impossible from your vocabulary. Keeping that word at bay ever since, a wide circle of people have fortified and inspired this book project each step of the way. Very certainly, its impossible to thank you enough.
In special, we are deeply grateful to Joy Glenner, for her shared remembrances of her husband and her enthusiastic support; to Caine Wong, for his scrupulous descriptions of the science in George Glenners lab; to Jim Gusella, for his considerable guidance and fact-checking, especially as pertains to the Huntingtons work; to Dennis Selkoe, for his close reading of several chapters, his helpful corrections, and his contribution of so many key details; to Bill Corner, for innumerable wise insights into the pharmaceutical world and for being a savvy mentor; to Robert Terry, for laying out the historical backdrop and for also being a savvy mentor; to Wilma Wasco, John Hardy, Mike Mullan, Jerry Schellenberg, Christine Van Broeckhoven, Dale Schenk, and John Breitner for their extensive input and review of certain sections; to Paul Raia, for his open-door counsel; to Jean-Paul Vonsattel, for his in-depth tutelage in neuropathology; to Kathleen Ottina, for her patient explanations; and to the triumvirate partnersSteve Wagner and Sam Sisodiaeach of whom lent large. We are indebted as well to Carmela Abraham and Dora Kovacs, for their insights and for permitting us to use their photographs. Posthumous tribute goes to Henry Wisniewski who left us with many valuable points of reference, as well as the mandate to tell some good stories.
The Noonan family gave this book the invaluable reality of what an at-risk family is faced with. To Julie, Pat, Malcolm, Eryc, Fran, and the others, including spouses, our great appreciation for sharing your lives and imparting your strength as a family to the rest of us.
If we have managed to pin down the details, we are indebted to still others: Mary Anne Anderson, Larry Altstiel, Mark Baxter, Merrill Benson, Katherine Bick, Deborah Blacker, Danny Chun, Alan Cohen, Linda Cork, Peter Davies, Kevin Felsenstein, Bias Frangione, Robert Katzman, Kevin Kinsella, Virginia Lee, Ivan Lieberburg, Toni Paladino, Huntington Potter, Richard Roberts, Kathleen Sweadner, John Trojanowski, Paul Watkins, Bruce Yankner, former SIBIA-ites, and all others who supplied expertise.
Our gratitude goes as well to the Special Collections staff at the University of California, San Diego, for making available George Glenners papers; to the Oral History Program, Department of Special Collections, University of California, Los Angeles, for granting permission to draw upon the oral history interview it conducted with Rudy for the Pew Scholars in the Biomedical Sciences Oral History and Archives Project of the Pew Charitable Trusts; and to the helpful librarians at Harvards Countway Library of Medicine and Boston Public Library.
Members of Mass Generals Genetics and Aging Unit deserve medals not only for their ready assistance, but for being so accommodating of this project. To Wilma Wasco, Dora Kovacs, Ashley Bush, Donna Romano, Tae-Wan Kim, Deirdre Couture, and Denise McDougalltremendous thanks to each of you.
Fortunately, another member of the above clan is Rob Moir, a protein chemist whose fine talent for computer graphics lends so much to these pages.
That this book actually took three-dimensional form is due to three ardent bookmakers. Thank you, Jeffrey Robbins, for your excitement over this project and for taking it on. Thank you, Doe Coover, for being such a discerning and nurturing agent. And thank you, Amanda Cook, for your wise decisions about content and for being such a first-class editor. The books production team, headed by Marco Pavia, made it all come together: large thanks for all your efforts.
When the word impossible especially threatened, family and close friends vanquished it. Please knoweach one of youhow much your steadfastness has meant.
RET & ABP
Introduction
Few real nightmares on earth compare to the terror wrought by Alzheimers disease. That this fatal brain disorder not only annihilates a persons mind, but starts doing so years before it takes their life is surely its most insidious aspect. Its initial symptoms of forgetfulness and personality changes lie so close to normalcy that they typically go unnoticed; and, once noticed, too long unexplained. As the victims grasp further slides, it can bring nothing but tormenting confusion for the patient and those close to him. What can be worse than watching someone you love cognitively flailing, until eventually they no longer recognize faces, surroundings, or even themselves?
More razor-sharp than Alzheimers physical distress is this emotional pain felt by patient and helpless bystanders. No one not saddled with it can understand it, not even my best friend, says Julie Noonan-Lawson. Along with her four sisters and five brothers, Julie watched their mother Julia Tatro Noonan succumb to a rare form of Alzheimers that strikes in middle age and is passed down to 50 percent, on average, of offspring. Consequently, all ten of Julias children, who currently span the ages of thirty-six to fifty-eight, bear the burden of being genetically at risk.
Framed in their recollections of their mother is how much she loved to sing. Growing up, they would cram into the family station wagon on hot summer days, swimsuits in tow, and led by Julias strong lilt sing one song after another full throttle all the way to Manomet Beach on Massachusetts South Shore. When, in her early forties, Julia inexplicably began singing less and lapsing into depressed moods, her children followed her into a mire of anxiety, trouble, and hurt. Her lost song was their lost song.
The Noonans response to the disease has been to not take it sitting down. So admirably, they and hundreds of other at-risk families have made invaluable contributions to research, helping the thousands of us who make up the Alzheimers scientific community to extrapolate the disorders molecular roots. Without their aid, the following account of the inestimable progress weve made in a remarkably short time wouldn t exist for the telling. Faced with the prospect of the diseases bull run through generations of their large family, the Noonans made their DNA available to investigators at Massachusetts General Hospital in Boston. Its primarily under that roof that Ive been involved in researching Alzheimers causes since the early-1980s, currently as the director of the Genetics and Aging Unit. From this vantage point emerges the following story. Although words cant fully describe the fears and losses an Alzheimer family is up against, some small sense of the Noonans ordeal appears between these chapters.
When a doctor recognized Julias illness in 1967, its brand of dementia was thought to be confined to middle age. It wasnt long before the true boundaries of Alzheimers emerged. Researchers realized that its classic lesionsthe microscopic amyloid, plaques and Neurofibrillary tangles
