PCFA - Printer Friendly - Alzheimer’s Research

A family with an astonishing rate of Alzheimer’s disease
may harbor a powerful new gene.

By Michele Cohen Marill — September 11, 2017

ELLIJAY, Ga. — Louise Lowman Lee remembers stories about her great-grandmother being put in a fenced area in the backyard, so she could wander safely. She watched her mother patiently care for her grandmother, who lost her reason, inhibitions, and ability to care for herself. Then Alzheimer’s disease gradually eroded the brain of her devoted mother, too.

But when Lee and two of her sisters brought their mother, Mildred Chastain Lowman, to Emory University in Atlanta in 2006, they weren’t thinking about the family tree. They were just looking for the best possible treatment.

Dr. Allan Levey asked them to come into a conference room with a genetic counselor and other members of his team. “We’ve been waiting for you,” he said.

“We were sort of stunned,” recalled Sherry Dunn, another sister. “We were looking at each other like, ‘What are they talking about?’”

Levey explained that he had seen other Chastains in his clinic over the years and had begun studying their pattern of Alzheimer’s inheritance. Genetic studies are stronger if they include multiple branches of a family tree, and here was Lowman, a distant cousin. She even looked uncannily like another Chastain patient Levey had treated.

Blessing from a Curse

By Mary Loftus

More than a decade ago, a woman in her early 70s came to see neurologist Allan Levey for an evaluation. She was experiencing progressive memory decline and was there with her children.

Part of the evaluation involved taking a family history. One of the woman’s sisters had died with dementia and an autopsy had confirmed Alzheimer’s disease. But it was the previous generation that captured Levey’s attention. Her father was one of nine children, and all had dementia. And three family members had had autopsies where Alzheimer’s was confirmed, says Levey, director of Emory’s Alzheimer’s Disease Research Center.

Already, genetics was a hot topic in Alzheimer’s research. A major “susceptibility gene” variant—ApoE4—had been discovered that increased one’s risk but was not sufficiently strong to cause the disease by itself.

For early-onset Alzheimer’s, which often strikes before age 60, even stronger genetic determinants had been discovered—three causal genes that were probably responsible for only a small number of cases, but which were autosomal dominant. If you had the gene, you would get the disease.

One such case involved a large Colombian clan from an isolated area in the Andes whose members were exceptionally prone to early-onset Alzheimer’s. Affected family members were discovered to have an altered protein on the presenilin-1 gene on chromosome 14—the Paisa mutation. Each child of a parent with the gene has a 50-50 chance of inheriting the trait. The New York Times and other media have done stories on the family and researchers have traveled from far-flung institutions to conduct studies on family members (one researcher survived a kidnapping by guerillas, who were persuaded to protect the blood samples by chilling them in a river.)

“This is the only place in the world,” said Francisco Lopera, the neurologist who discovered the Paisa mutation, “where we can find a family like this.”

Which may no longer be true.