Researchers are studying families for clues to how Alzheimer’s develops
January 6, 2017
||Lizeth Navarro at her home in La Habra, California, on Dec. 22, 2016. The 19-year-old chemical engineering major decided to attend college nearby partly just to keep an eye on her mother. She hasn’t decided whether to get tested for the mutation herself. Photo by Heidi de Marco/KHN
||John Kitchen listens as his wife, Michelle Lopez, expresses her fears about the future after the Alzheimer’s presentation in Colton, California, on Nov. 22, 2015. Photo by Heidi de Marco/KHN LA HABRA
Rosemary Navarro was living in Mexico when her brother called from California. Something wasn’t right with their mom, then in her early 40s. She was having trouble paying bills and keeping jobs as a food preparer in convalescent homes.
Navarro, then 22, moved back to the U.S. with her two young children.
Before long, Navarro was feeding her mom, then changing her diapers. Near the end, her mom, a quiet woman who had immigrated to the U.S. as a teenager and loved telenovelas, could communicate only by laughing or crying. She died at 53 in a nursing home.
It has happened again and again in her family — relatives struck by the same terrible disease, most without any clue what it was. An aunt, an uncle, a cousin, a grandfather, a great grandfather. “Too many have died,” Navarro said. All in their early 50s.
Now the family knows the reason for their curse: It’s a rare type of early-onset Alzheimer’s disease, caused by what’s come to be known as the “Jalisco” genetic mutation. Doctors today can tell someone they have it but can’t stop its destructive march.
For Navarro, watching her relatives succumb is like looking into a crystal ball, one she wants to hurl across the room. She, too, has the mutation. This year, she turned 40 — the same age her mother was when she started wandering off and forgetting simple things.
“I don’t look forward to birthdays,” she said. “I didn’t want to celebrate 40, much less 41.”
SPARING THE NEXT GENERATION
Navarro belongs to an exclusive but unenviable club whose members are genetically programmed for early memory loss and death.
Of the more than 5 million people across the U.S. who have Alzheimer’s, about one percent have genetic mutations that are known to cause the disease. Navarro’s gene is known as the Jalisco mutation because it is believed to have surfaced first in that Mexican state. Roughly 50 families are known to have it.
Cases like Navarro’s are of great interest to Alzheimer’s researchers. Studying this unique population with genetic mutations, they say, could help unlock some of the biggest mysteries of the more common form of the disease: How does it develop? What can be done to stop it?
Ordinarily, it’s difficult — if not impossible — to predict Alzheimer’s. But with these families, researchers know the mutation carriers will get the disease. They also know approximately when symptoms will appear, so they can get a real-time look at how the disease develops and possibly design drugs for it before patients lose their memory.
“If you know from age 18 or even from birth whether someone is going to develop the disease or not, you have got a big window to intervene,” Navarro’s doctor, John Ringman, a neurology professor at the Keck School of Medicine of the University of Southern California. “We don’t have a way to repair or bring back lost brain cells.”
Hundreds of people whose families are afflicted with a variety of early-onset mutations are subjecting themselves to medical tests, hoping scientists can develop therapies to prevent and treat Alzheimer’s. But their participation often comes with the sad realization it may be too late to help them.
More than 450 people are part of an international network of research being led by Washington University School of Medicine in St. Louis. Each has a parent with an early-onset gene mutation.
“They are all desperately fearful that they themselves have inherited a mutation,” said John C. Morris, director of the school’s Alzheimer’s Disease Research Center. “But what they are really fearful about is that if they did, that they will pass it along to their children.”
Children have a 50 percent chance of inheriting the mutation from a parent who carries it.
Navarro, whose children are now young adults, is well aware of the statistics. She has joined the network’s research effort, of which Ringman is a part. Last year, a scan showed her brain had already started to shrink — a sign that the disease was taking hold.
‘AT LEAST WE KNOW NOW’
Last November, Dr. Ringman drove to Colton, Calif. — 60 miles east of Los Angeles — to meet with the large and close-knit Kitchen family. Jay Kitchen and his younger brother John had been referred to him after each suffered a series of baffling symptoms.
It had started about four years earlier. Jay, then a 44-year-old sports writer, began having difficulty speaking. He felt off balance and was forgetting things. Soon afterward, his younger brother, John, a high school history teacher, started becoming easily confused. He would forget what day it was and how to get to the market.
Doctors were “scratching their heads trying to figure out what was wrong,” said the brothers’ aunt, Linda Ramos.
A neurologist referred the brothers to Ringman, who ordered a blood test. On this November morning, Ringman came to Ramos’ home, where the extended family was gathered, with grim news. Both men had the Jalisco mutation. The brothers sat in near silence, Ramos said.
Like many families Ringman encounters, the other relatives also absorbed the news with little emotion or surprise — as though the doctor were confirming nameless fears.
“My thought was, ‘At least we know now,” Ramos said. “Finally, we know. Thank God we have a name [for it] and maybe we can do something for their kids.”
ONE FAMILY LEADS TO ANOTHER
Ringman was a young neurologist at the University of California, Irvine in 1999 when a 42-year-old woman, Rosa Maria Navarro, came to see him. Her daughter Rosemary brought her, distraught because her mother, like so many other relatives, had signs of early Alzheimer’s.
Ringman was aware of recently identified familial Alzheimer’s mutations and immediately suspected Rosa Maria had one. She tested positive for the mutation later named Jalisco.
Soon afterward, another patient of Ringman’s, also with forebears from Jalisco, tested positive for the same mutation.
Ringman started working with doctors in Mexico, and they identified many similar patients who were all at least distantly related. They concluded the disease likely started with one ancestor.
Ringman saw the tragedy but also the scientific opportunity in these discoveries. He later joined the Washington University research network in its quest for knowledge and treatment options.
Among the network’s early findings: The brain begins to change before any symptoms occur. The research essentially has presented a timeline of brain changes leading up to cognitive decline and has helped scientists decide when and where to aim drugs.
The Kitchen brothers are not participating in the research. Both are declining precipitously. Jay only occasionally recognizes family members. John can still hold a conversation but struggles for the right words.
“We get a glimmer of hope,” their aunt Ramos said, “but then we think we are foolish for even hoping.”
FEAR AND FAITH
Navarro’s 19-year-old daughter, Lizeth, and her 22-year-old son, Ricardo, live with her in a three-bedroom trailer in La Habra. Both say said their mom has started forgetting little things. — the movie they saw last week or what they need from the grocery store.
Rosemary Navarro keeps working in customer service and tries to focus on her family, not the disease. “I can’t let it overcome me,” she said.
She’s joined a drug trial out of Washington University. Each month, a nurse visits and injects a medication, which she’s pretty sure is not a placebo.
“I have to have faith in the drug,” she said. “That’s my only solution for now.”
She didn’t finish her thought.