Alzheimer’s ‘escapees’ may offer research clues
Some patients don’t develop disease despite genetic predisposition
Doug Whitney inherited the same gene mutation that gave Alzheimer’s disease to his mother, brother and generations of other relatives by the unusually young age of 50.
Yet he’s a healthy 73, his mind still sharp. Somehow, the Washington man escaped his genetic fate.
So did a woman in Colombia who dodged her own family’s similar Alzheimer’s destiny for nearly three decades.
To scientists, these rare “escapees” didn’t just get lucky. They offer an unprecedented opportunity to learn how the body may naturally resist Alzheimer’s.
“It’s unique individuals oftentimes that really provide us with breakthroughs,” said Dr. Eric McDade of Washington University in St. Louis, where Whitney’s DNA is being scoured for answers.
The hope: If researchers could uncover and mimic whatever protects these escapees, they might develop better treatments — even preventive therapies — not only for families plagued by inherited Alzheimer’s but for everyone.
“We are just learning about this approach to the disease,” said neuropsychologist Yakeel Quiroz of Massachusetts General Hospital, who helped study the Colombian woman. “One person can actually change the world — as in her case, how much we have learned from her.”
Quiroz’s team has a pretty good idea what protected Aliria Piedrahita de Villegas — an additional genetic oddity that apparently countered the damage from her family Alzheimer’s mutation. But testing showed Whitney doesn’t have that protective factor so something else must be shielding his brain.
Now scientists are on the lookout for even more Alzheimer’s escapees — people who may have simply assumed they didn’t inherit their family’s mutation because they’re healthy long after the age their loved ones always get sick.
“They just think it’s kind of luck of the draw, and it may in fact be that they’re resilient,” said McDade, a researcher with a Washington University network that tracks about 600 members of multiple affected families — including Whitney, the escapee. “I guess that made me pretty special. And they started poking and prodding and doing extra testing on me,” the Port Orchard, Wash., man said. “I told them, ‘You know, I’m here for whatever you need.’ ” Answers can’t come quickly enough for Whitney’s son Brian, who also inherited the devastating family gene. He’s reached the fateful age of 50 without symptoms but knows that’s no guarantee.
“I liken my genetics to being a murder mystery,” said Brian Whitney, who volunteers for Washington University studies that include testing an experimental preventive drug. “Our literal bodies of evidence are what they need to crack the case.”
More than 6 million Americans, and an estimated 55 million people worldwide, have Alzheimer’s. Simply getting older is the main risk — it usually affects people over age 65.
Less than 1% of Alzheimer’s is caused by inheriting a single copy of a particular mutated gene. Children of an affected parent have a 50-50 chance of inheriting the family Alzheimer’s gene. If they do, they’re almost guaranteed to get sick at about the same age as their parent did.
That near certainty allows scientists to study these families and learn critical information about how Alzheimer’s forms. It’s now clear that silent changes occur in the brain at least two decades before the first symptoms — a potential window to intervene. Among the culprits, sticky amyloid starts building up, followed by neuron-killing tau tangles.
What happens instead in the brains of the resilient?
“That’s why I’m here,” said Doug Whitney, who for years has given samples of blood and spinal fluid and undergone brain scans and cognitive exams, in the hunt for clues. “It’s so important that people in my situation come forward.”
Whitney’s grandparents had 14 children and 10 of them developed early-onset Alzheimer’s. The first red flag for his mother: Thanksgiving 1971, when she forgot the pumpkin pie recipe she’d always made from memory.
“Five years later, she was gone,” Whitney said.