Advances in the DIAN Research

On November 16, in St. Louis, I shared the Reiswig family story, The Thousand Mile Stare: One Family’s Journey Through the Struggle and Science of Alzheimer’s, with several hundred concerned, attentive people. Sharing the program with me were Dr. John Morris and Dr. Randall Bateman of Washington University in St. Louis. They head up the DOMINANTLY INHERITED ALZHEIMER’S NETWORK (DIAN), an international research project involving people who are in line for any of the three known genes that cause Familial Early Onset Alzheimer’s Disease. Here’s what I learned from the meeting, and from a conversation with Dr. Bateman after the meeting.

The DIAN research stands poised to move beyond the IDENTIFICATION OF BIO-MARKERS of Alzheimer’s into a STUDY OF TREATMENTS for the disease. After the expected approval by the FDA, this opportunity to study potential treatments will happen nearly fifty years from the time my Aunt Ester May first said in the late 1960s, “Our family must pray, but we must also get involved in medical research.”

The DIAN research is designed to help both the people facing the genetic form of Alzheimer’s as many in my family are, and, ultimately, all people who face the ravages of Alzheimer’s disease.

Any interested person can contact the DIAN project, Wendy Segurdson:
sigurdsonw@wustl.edu
314.362.2256

Or contact me: gdreiswig@yahoo.com.

THE END

Boston Globe Bestsellers: Sept. 26-Oct. 3

Hardcover Nonfiction (LOOK WHO'S AT #5)

1. Earth (The Book)
By Jon Stewart. Grand Central.

2. The Grand Design
By Stephen Hawking and Leonard Mlodinow. Bantam.

3. The Warmth of Other Suns
By Isabel Wilkerson. Random House.

4. Sh*t My Dad Says
By Justin Halpern. It.

5. The Thousand Mile Stare
By Gary Reiswig. Nicholas Brealey.

6. A Journey (tie)
By Tony Blair. Knopf.

6. Let’s Take the Long Way Home
By Gail Caldwell. Random House.

6. The Power
By Rhonda Byrne. Atria.

6. The Big Short
By Michael Lewis. W. W. Norton.

10. Outliers
By Malcolm Gladwell. Little, Brown.

REPORT FROM THE RESEARCH FRONT

Since the discovery in 1984 that the plaques found in the brains of people with Alzheimer’s was made up of Beta Amyloid Protein, it has been assumed by many that Beta Amyloid was a major cause of the disease. More than 7,000 research papers have been written, most assuming Beta Amyloid plays a major role in the development of Alzheimer’s. Recently, this has been demonstrated to be true, but not in the way many researchers expected.
Within the past few months, Alzheimer’s research has been rocked with news about the ineffectiveness of experimental treatments that prevent the formation of, or reduce the amount of, plaque in the brains of people living with Alzheimer’s. Because of these failures, the Manhattan chapter of the Alzheimer’s Association brought together five prominent researchers who discussed, PARADIGM SHIFTS IN ALZHEIMER’S RESEARCH: IMPLICATIONS FOR DIAGNOSIS AND TREATMENT. Here’s some of what I learned at the two-hour presentation.
Instead of causing the disease, plaques in the brain apparently result from an immune response, an attempt to fight off disease. This explains why the treatments in research models that lowered the amount of visible plaque actually made patients worse. It could also explain why some people who show a large amount of plaque in their brains do not have symptoms of dementia.
Several research projects will now focus on oligomers, a more soluble form of the protein, while other researchers will concentrate on tau, the other prominent protein comprising the neurofibulary tangles, the second, long recognized abnormal accumulation found in the brains of people with Alzheimer’s. The search is now on for a compound that will attach to and identify oligomers, similar to the radio-active compounds that currently can be used to find Beta Amyloid in the brain.
The more than sixty private companies involved in Alzheimer’s research have spent billions of dollars trying to find an effective treatment, but, so far, major advances have eluded everyone. However, the point is well taken that each setback is an advance in knowledge. The positive news is twofold: Beta Amyloid does not appear to be the culprit it was once thought to be, and is not likely the key to prevention of the disease, so attention can now be focused elsewhere; and, the private companies, in addition to publicly funded laboratories, are all still involved in trying to find answers despite the fact their investments so far have brought no financial rewards.
One researcher quipped, “We’ve cured a lot of animals (rats and mice) that we’ve purposefully infected with Alzheimer’s. We’re making progress.” Another observed, “Apparently, it is easier to send a man to the moon than to find an effective treatment for Alzheimer’s. That’s how complex the disease is.”
Mary Sano, PhD, director of the Alzheimer’s Disease Research Center at the Mount Sinai Hospital School of Medicine, observed that more volunteers are needed to participate in research. She reminded everyone that the Alzheimer’s Association has a program to match volunteers with appropriate ongoing research. www.alz.org.

READING TONIGHT!!

Meet the Author Gary Reiswig
Learn What's New in Alzheimer's Disease Research

Join us for this moving and
inspiring event.

For more information, contact Irene Hammer-McLaughlin, Associate Director, Alzheimer's Association, via e-mail or at 617.393.2052.

We look forward to
welcoming you.

World Alzheimer's Day
Tuesday, September 21st, 2010
6:30 pm

Border's Bookstore
511 Boylston Street
Boston, MA 02116


From Gary Reiswig's story of his ancestral roots in a small German Town, to Dr. Alois Alzheimer's discovery of the disease, to the Reiswig's triumphs and tragedies on their Oklahoma farm, to a modern-day congressional hearing room, this book offers profound insight into the devastating world of Alzheimer's, and hope for the development of a cure.

Gad Marshall, MD will join us to share his insights. Dr. Marshall is Associate Neurologist, Associate Medical Director of Clinical Trials at the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital and Assistant in Neurology at Massachusetts General Hospital.

5.3 million individuals in this country have Alzheimer's Disease - more than 200,000 of these individuals are under the age of 65. One in eight baby boomers is at risk.

Important step forward, proteins in spinal fluid as markers, may help diagnose/treat Alzheimer's.

http://www.cbsnews.com/stories/2010/08/09/eveningnews/main6757986.shtml?tag=cbsnewsTwoColUpperPromoArea

ACCURATE ALZHEIMER’S DIAGNOSIS NOW, TREATMENT NEXT

A giant step forward in the diagnosis of Alzheimer’s disease was announced in a front page article in The New York Times on June 24. A private company, Avid, working with a radio active compound patented by the University of Pennsylvania, can identify exactly which patients have plaques (clumped protein) in their brains, one of the primary pathological signs of Alzheimer’s. The ability to identify the plaques may allow physicians to begin treatment of the disease earlier, as well as enable researchers to study the effectiveness of new treatments.

PiB was the first such radio active compound used to photograph brain plaque. It was developed and tested at another Pennsylvania University, the University of Pittsburgh. As described in THE THOUSAND MILE STARE: One Family’s Journey Through the Struggle and Science of Alzheimer’s, my family, and any person who may be in line to inherit one of the three known younger onset Alzheimer’s genes, can be involved in the research (DIAN) that uses PiB to study the development of Alzheimer’s. The new compound used by Avid employs a radio active formula that is already used for about two million cancer scans a year so is more accessible for use by physicians who deal with Alzheimer’s patients of all ages.

Although it appears Avid will soon be able to market its test, it is not yet known if the screening can be made affordable for all patients who might benefit. There’s also a larger question. Using the scan, how long will it take to study and identify new, more effective, treatments? Despite these questions, a major advance in the war on Alzheimer’s has been made.

My Latest Interview

http://www.dispatch.com/live/content/life/stories/2010/03/23/family-struggles-with-gene-that-causes-alzheimers.html?sid=101

Author of 'Thousand-Mile Stare' recounts tragedy of his family's early-onset Alzheimer's

Gary Reiswig was 25 when he discovered that his father had an inherited form of early-onset Alzheimer's disease.

The illness had destroyed most of his family's previous generation. And the Oklahoma native had a 50-50 chance of inheriting the mutated gene.

It would be more than 30 years before he would learn that he had won that genetic coin toss.

Reiswig, now 70, chronicles his family's quest for answers in The Thousand Mile Stare: One Family's Journey Through the Struggle and Science of Alzheimer's (Nicholas Brealey Publishing, $22). The family's research participation, led by a determined Aunt Ester May, resulted in the discovery of a key genetic marker for Alzheimer's, believed to be traced to Reiswig's Volga German ancestors.

Over the years, his father and nine of his 14 siblings were afflicted with the disease. They often displayed symptoms in their 40s. Before he learned his own fate, Reiswig had even plotted his suicide to spare his family.

Reiswig, who will appear today at Legacy Books in Plano, spoke by phone from his home in Eastern Long Island, N.Y.

How did you hear or see Alzheimer's affect your family?

There was an observed family rumor that my great-grand- father Christian was senile by age 43. He died in 1903. I knew my grandfather well. I would hold his hand on walks so he wouldn't get lost. He got to where he couldn't speak and was silent with "the thousand-mile stare." My dad's oldest sister, Pearl, would put the ice tray in the stove instead of the fridge. She grew angry and violent and had to go into a care facility. Another of my dad's younger sisters got so disoriented and forgetful she could not take care of her son, who had to live with relatives. ... One of the largest impacts of this disease is that, when we finally understood what was happening, it blew our family apart.

What have you learned about the thousand-mile stare?

One of my cousins describes it as periods of white static – when his brain stops functioning. He doesn't know how long these moments last, but he will sometimes check to see if he was acting funny, and his wife will give him feedback. That is my theory with my grandfather. I believe he had one of those moments of white static that caused the original wreck with a train that killed my grandmother in 1936.

What can we learn about the disease, which is largely not driven by genes, from the inherited early-onset families?

Since the symptoms and the pathology and progression are so similar to later-onset, scientists feel younger people who are affected make better research subjects – they are an isolated population without so many other variables. It is truly a dynamic field. ... The next research of the Alzheimer's brain has to do with whether the proteins are the cause of the disease or the result of the disease. ... If they are the cause of the disease and you can stop the development, that would be a way to approach treatment.

What was the moment like when you found out you essentially won the genetic coin toss?

I had sent my blood into the Alzheimer's Disease Research Center inSeattle. ... There was an article about our family, including a chart of my generation. My brother, sister and I were included because we had been vocal about wanting to participate. I could see from that chart inScience magazine that I did not have the gene. There was my white box in the middle, between the black boxes of my older sister and younger brother. ... For my kids, it meant they didn't have to worry, they were free to find their own problems.

Helen Bond is a freelance writer in Dallas.

healthyliving@dallasnews.com

The Thousand Mile Stare: A Conversation with Gary Reiswig

My friend Chuck Jackson was diagnosed with young onset Alzheimer’s disease at age 50. It wasn’t a total surprise to him – his brother was being treated for Alzheimer’s and many of his cousins had it. His mother and at least nine of her siblings had it. Most had symptoms early in midlife; some died while still in their 50s. Chuck and many of his relatives have a rare genetic variation called presenilin 2, or PS2, that almost guarantees a person will develop Alzheimer’s.

It’s only recently that the stigma attached to dementia has lessened. For a long time, Chuck’s relatives didn’t talk much about their family history. But since his diagnosis in 2004, Chuck has talked with support groups, participated in research and testified before Congress.

His cousin Gary Reiswig, who now knows he does not carry the PS2 gene variation, has gone even more public about the disease that has ravaged his family. His new book,The Thousand Mile Stare: One Family's Journey through the Science and Struggle of Alzheimer's, is a very personal journey through generations of disease and tragedy.

The book opens in 1936, when Gary and Chuck’s grandfather, perhaps in the early stages of Alzheimer’s, drove his truck into the path of an oncoming train in rural Oklahoma. He and one of his sons were injured, and his wife was killed. From that story, so emblematic of the family’s problems, the book spans two continents and more than two hundred years. The family’s roots as “Volga Germans” who left Germany to farm land along the Volga River in Russia in the 1700s are interesting, but it’s the little details of daily life with Alzheimer’s that make this book so riveting.

Shattered and Scattered by Disease

Reading the book, I was struck at how hard life would have been for the Reiswigs even without Alzheimer’s. Life on the farm wasn’t easy, and they had to deal with wars, the Great Depression and the Dust Bowl. Did enduring these hardships, especially the Dust Bowl, shape how the family has dealt with Alzheimer’s?

Gary Reiswig

“I think the Dust Bowl was the least of it,” Gary says. “Going back to when my family left Germany and went to Russia, they spent 110 years living in a small German enclave surrounded by people they were suspicious of and who were suspicious of them. So they had this cultural legacy – a sense of isolation. Then when they came to the U.S., they were exposed to a broader community and tried to adjust to their new situation. They even gave up their religion and became Seventh-day Adventists. They adopted this new religion full force and were prominent in the church for a generation or two. In my dad’s generation, with World War I and World War II, they stopped speaking German at home. They really tried to fit in.”

“But in that same generation, people lived long enough for the disease to rear its ugly head,” he says. “The symptoms became apparent in Dad and three of his siblings almost simultaneously. The neighbors began to realize that the Reiswigs were ‘a little crazy.’ To develop this kind of reputation in a community where they were trying to fit in was devastating, and really led to the way my family has scattered. When I was a kid, most of my family lived within a few miles of each other. But now I have only one relative there, and she is basically comatose in a nursing home. So the Dust Bowl, depression and wars were bad, but the events after the late 1930s, when my granddad drove his truck through the railroad crossing and my grandmother was killed, were much more ominous.”

Finding Meaning

Along with many family members, Gary gave blood samples for research in the 1980s. But it was only when he saw a diagram of the family tree published in a scientific journal in 1995 that he understood he did not have the PS2 gene. His father, brother and sister and many of his cousins have now died of Alzheimer’s, and he describes himself as “the last man standing.” He says it took some time to find meaning amidst all this sickness and death.

“After my father died and the reality hit me that I was possibly next in line, I became imbued with some sense that life had speeded up,” he says. “I felt I needed to try to do EVERYTHING in anticipation that my life could be cut short. In retrospect, I think that was probably an overreaction. A more appropriate reaction might have been to try to stay in the moment, to concentrate and to not try to do so many things. I regret that I let myself be spurred into trying to do so many things, not gaining the expertise I really wanted in areas like writing. In essence, the disease has finally given me a direction and purpose for the rest of my life: writing about the disease, and helping my family and others who are facing the same quandary I was facing.”

A Long Haul to the Cure

Along with each generation’s stories, Gary writes about Alzheimer’s research, from Alois Alzheimer’s description of the plaques and tangles in the brain of a young onset dementia patient in the early 1900s to the immunotherapy and imaging studies Chuck is participating in. Sorting through the research has made Gary more realistic about progress towards a cure.

“Every day you see some article about Alzheimer’s research, and it sounds so good,” he says. “But it’s one little piece, one little aspect. What I learned talking with researchers is that we’re still looking at a long haul.”

If you’re interested in Alzheimer’s research, or simply want to know more about this extraordinary family, I recommend The Thousand Mile Stare.

ARF Notable Book: The Thousand Mile Stare, by Gary Reiswig

20 January 2010. Gary Reiswig has variously been a young farmer, preacher, Ph.D., city planner, innkeeper, real estate agent, and author. He will always be a member of the “Volga Germans.” Through their research participation, this extended family made possible the identification of presenilin 2 on chromosome 1 (Levy-Lahad et al., 1995; Rogaev et al., 1995; Levy-Lahad et al., 1995) as the third gene known to cause autosomal-dominant Alzheimer disease, and the term Volga Germans became a fixture in AD genetics. Reiswig tells a harrowing tale, interweaving chronological chapters of his family’s and personal life story with snapshots of how the field of U.S. Alzheimer’s science evolved in those same years. This book offers something for everyone among the diverse Alzforum audience of researchers and related professionals, caregivers, and early-stage patients themselves. Scientists will find a compassionate inside story of what goes on in families stricken with eFAD, and the story features some of their familiar colleagues, including Thomas Bird, Gerry Schellenberg, Rudy Tanzi, and Bill Klunk. To families and AD activists, the book validates their own experience. It offers an account of what they have achieved to date in the way of bringing their issue before Congress and to the national media. These readers may recognize Chuck Jackson (statement to Congress), a cousin of Reiswig’s who lives with AD and works to raise public awareness. The book creates moments of dread when Reiswig realizes that AD is beginning to claim members of the next, younger generation. Some of these moments echo past tragedies. For example, while driving across the wide open prairie of the Oklahoma panhandle, Reiswig’s grandfather, a farmer, overlooked an oncoming train. The train killed his wife, a mother of 14 children. Reiswig attributed this accident to a mental lapse during his grandfather’s early-stage AD. Four decades later, Reiswig asks his father to drive across several states to help his own young family move house. His father gets utterly lost, returning home to the family farm days late and plunging Reiswig into guilt over having denied his father’s condition. And three decades later still, after Reiswig’s siblings and cousins have been decimated by AD, his nephew, who has taken over the family farm, causes a car accident amid subtle symptoms of forgetting and confusion. This nephew is about to become a young grandfather, extending a line of life at risk for early-onset AD. This family is hit hard. Of Reiswig’s 13 aunts and uncles, only three escaped the mutation. His brother and sister both died young from AD. Going back in history, Reiswig cites speculation by Tom Bird of the University of Washington, Seattle, that Alois Alzheimer’s famous patient Auguste Deter herself might have been a distant relative of the Reiswigs, as his ancestors emigrated to Russia from a region near Frankfurt, Germany, where Deter lived. The author touches on themes that frequently come up in conversation with families living with eFAD. While the disease prompts some relatives to pull close, its taboos and the burden it imposes also tear families apart. Reiswig notes how he left home as early as he could, having watched his grandfather’s final years as a young child and seeing as a teenager how his own dad was starting down the same road. Others fled, causing a tight family that had settled in the rural heartland to scatter to both U.S. coasts and Australia, as if trying to outrun a fate that was sealed at conception. Reiswig also describes vivid vignettes of how early symptoms—loss of skills, lapses in judgment—manifest in able farmers and craftsmen who were increasingly stumped trying to repair their machinery, or made ill-advised purchases. The book’s title evokes a sign that relatives and dementia clinicians know well—that long, forlorn stare into the distance, that glance where the person behind the eyes is strangely missing. Incidentally, a new study out this week formally characterizes staring and mental lapses as an early sign of Alzheimer disease (Escandon et al., 2010). Many readers will find food for thought in Reiswig’s description of how the family tried to move past denial toward a more proactive stance, and the attendant effort to become engaged in research. As is often the case, one relative—strong-willed aunt Esther May—drove this move toward openness in the Reiswig family. She drew the scorn of some relatives but managed to address Congress in testimony that contributed in the 1970s to the initiation of the country’s system of federally funded Alzheimer’s Disease Research Centers. At several points in the book, Reiswig describes the Dominantly Inherited Alzheimer Network (DIAN) study, a much more recent research initiative that is currently enrolling participants. DIAN invites relatives of families with autosomal-dominant AD to join an international registry of longitudinal research to understand and treat the presymtomatic decade of AD, where pathology builds up in the brain. That is the time before people develop mental lapses and the thousand-mile stare. (For more information on DIAN, see ARF related news story; Dominantly Inherited Alzheimer Network (DIAN).) But also, as Reiswig recounts how for decades he lived in fear of developing AD himself, he mentions that he found out he had escaped the mutation only by seeing his family’s pedigree printed in Science magazine, which he, a Long Island innkeeper at the time, obtained after reading about the presenilin 2 discovery in The New York Times. His research participation apparently had not triggered information back that the family’s gene had been found and his family tree was about to be published with this pertinent information in it. This was in 1995. Since then, scientists have wrestled with the issue of information sharing with research participants, and a consensus is growing that ways must be found to communicate with research volunteers more fully. Published by Nicholas Brealey and widely available online, this short book would have benefitted from rigorous editing to iron out some weaknesses in the scientific sections, but it remains well worth a read. For a special section of Alzforum dedicated to this form of Alzheimer disease and the families who live with it, see Early-Onset Familial AD.—Gabrielle Strobel.

AUTHOR REISWIG AND DR. SHELLENBERG EXPLORE ALZHEIMER’S DISEASE in URSINUS PROGRAM MARCH 2

COLLEGEVILLE, Pa. -- Author Dr. Gary Reiswig will read from his newly published memoir. The Thousand Mile Stare: One Family’s Journey through the Struggle and Science of Alzheimer’s March 2 during a program in Bomberger Auditorium on the Ursinus College campus. The event is free and open to the public.

He will appear with Dr. Gerard Schellenberger of the Department of Pathology and Laboratory Medicine at the University of Pennsylvania School of Medicine, who figures prominently in Reiswig’s book. The Reiswig family’s relationship with Dr. Schellenberger’s team led to breakthrough discoveries, such as a blood test to detect a gene that could cause early onset Alzheimer’s disease. The program promises to offer insight into the life of family with a loved one suffering from the disease.

In the book, published by Nicholas Brealey Publishing, Reiswig chronicles his family’s mysterious behavior and history, their discovery of Alzheimer’s in the family, and their involvement with the medical community which led to the discovery of a key genetic marker.

Reiswig, who was born in the Texas panhandle, was ordained as a minister. He saw his grandfather and father exhibit the effects of Alzheimer’s disease. He left the ministry at 30, earned a Ph.D., worked as an educator and city planner in Pittsburgh and began writing. His novel, Water Boy, was published by Simon & Schuster. After his sister and brother died in their 50s from early onset Alzheimer’s disease, he began collecting information for The Thousand Mile Stare. The book, which The book .will be available for purchase at the lecture.

For the past 18 years, Dr. Schellenberg has worked on the genetics of Alzheimer’s disease, starting with ground-breaking research on early-onset familial Alzheimer’s disease followed by work on late-onset dementia which is where much of his current effort is focused. He is founder and head of the Alzheimer’s Disease Genetics Consortium supported by the National Institute on Aging. He also worked on the genetics of aging and on the molecular genetics on other neurodegenerative disorders related to Alzheimer’s disease.

Dr. Schellenberg leads the Alzheimer’s Disease Genetics Consortium (ADGC), which is comprised of a group of investigators who are using genome-wide association analysis methods to identify Alzheimer’s disease. He received his Ph.D. in biochemistry from the University of California, Riverside in 1978. Dr. Schellenberg joined the University of Pennsylvania faculty in 2008 where he is presently a Professor in the Department of Pathology and Laboratory Medicine. He has received numerous awards for his research.

Ursinus College is a highly selective, independent coeducational liberal arts college located on a scenic, 170-acre campus, 28 miles from Center City Philadelphia. The college is one of only eight percent of U.S. Colleges to possess a chapter of Phi Beta Kappa.

ALZHEIMER'S AGE OF ONSET, CAUSES, IMPLICATIONS

When the University of Washington's Alzheimer's Disease Research Center did its study of dominantly inherited Alzheimer's disease, looking for the gene that affects our family and other Volga German families (families who left Germany in the 1760's, lived in Russia along the Volga for a hundred years or more, then came to North America), they ultimately identified 11 VG families with familial Alzheimer's who carry the PS2 gene. The study showed a wide variation in the average age of onset within the 11 families. Our family's average age of onset was 51, and there was one family with an age of onset in the early 70's. The primary cause of this variation in age of onset is another gene. It is ApoE4. This gene is not the only factor. There are likely other genes with less impact on the age of onset than ApoE4. Two new ones have recently been identified that may act in conjunction with ApoE4.

Each child inherits one Allele of ApoE, either 2, 3, or 4, from each parent. Number 2 seems to be positive, increases the average age of onset of Alzheimer's, number 3 seems to be neutral, and number 4 lowers the age of onset. ApoE4 was very prominent in my father's generation, and seems to account for the low average age of onset of the disease. Many of that generation had two 4's. Such was the case with Uncle Oliver, who did not have PS2, but had clear symptoms of Alzheimer's by age 68 and died at 78.

My dad was 100% Volga German. Both his father and mother carried at least 1 ApoE4 and so they passed either 1 or 2 to the next generation. My dad's great, great grandchildren are now being born. They are only 1/16 Volga German. While that does not affect whether or not one inherits the dominant PS2 gene, it seems probable that the frequency of ApoE4's in the family has decreased dramatically since my father's generation, theoretically raising the age of onset of Alzheimer's caused by PS2. This may not be a total comfort to those in line for PS2. However, having symptoms at age 65 is certainly better than at age 55. If this hypothesis is true, the age of onset in our family is rising, the change could be a factor in such decisions as whether or not to have children and whether or not to be tested for PS2.

ApoE does not cause Alzheimer's. It is a "susceptibility" gene, increasing the likelihood that the one who carries the gene will get Alzheimer's, but not everyone who has the gene gets the disease. This gene appears to be affected by environmental factors, as well as by other factors unknown. Dr. William Klunk of the University of Pittsburgh pointed out in his endorsement of THE THOUSAND MILE STARE that nearly 50% of people who reach the age of 85 have Alzheimer's. In my case, I have 1 copy of ApoE4 so I have approximately a 50/50 chance of having Alzheimer's by age 80 instead of 85.

For me, the additional time I gained when PS2 skipped me seems like bonus time. While I don't relish the thought that ApoE4 may lower the age of onset if Alzheimer's comes, I want to make the most of the time I have. That's the least we can do to honor those who have already suffered and died.