Ione and Doug Whitney, February, 2025.
Megan Farmer, WashU Drugs
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Megan Farmer, WashU Drugs
Individuals who inherit one very uncommon gene mutation are nearly assured to develop Alzheimer’s earlier than they flip 50.
Apart from Doug Whitney.
“I am 75 years previous, and I feel I am functioning pretty effectively,” says Whitney, who lives close to Seattle. “I am nonetheless not displaying any of the signs of Alzheimer’s.”
Now a crew of scientists is making an attempt to know how Whitney’s mind has defied his genetic future.
“If we’re capable of be taught what’s inflicting the safety right here, then we may translate that to therapeutic approaches and apply that to the extra widespread types of the illness,” says Dr. Jorge Llibre-Guerra, an assistant professor of neurology at Washington College College of Drugs in St. Louis.
One chance is excessive ranges of warmth shock proteins present in Whitney’s mind, the crew reviews within the journal Nature Drugs.
There are hints that these proteins can stop the unfold of a poisonous protein that is among the hallmarks of Alzheimer’s, Llibre-Guerra says.
A genetic shock
Early-onset Alzheimer’s is all over the place in Whitney’s household.
His mom and 11 of her 13 siblings all had the illness by about age 50. “None of them lasted previous 60,” Whitney says.
Whitney’s spouse, Ione, noticed this up shut.
“We went residence for Thanksgiving, and his mother could not bear in mind the pumpkin pie recipe,” she says. “A yr later after we went again, she was already wandering off and never discovering her approach again residence.”
The affected relations all carried a mutated model of a gene known as presenilin 2. The variant causes an individual’s mind to build up beta amyloid and phosphorylated tau proteins, the hallmarks of Alzheimer’s.
When Whitney turned 60 and nonetheless had no signs, he assumed he did not have the mutation. However he wished to assist others. So he volunteered for a research of households with early Alzheimer’s.
“I submitted my blood samples and to my nice shock, it got here again constructive for the Alzheimer’s gene,” Whitney says. “It was fairly a shock.”
It was additionally a shock for scientists. Whitney was solely the third particular person identified to have escaped the consequences of a presenilin mutation.
The primary two got here from a gaggle in Colombia with mutations to the presenilin 1 gene. Whitney is the one particular person identified to have resisted a mutation within the presenilin 2 gene, which is discovered on a special chromosome.
All three had a lot of beta-amyloid of their brains. However surprisingly, they did not have a lot phosphorylated tau.
This type of tau is a misfolded protein that tends to look in a single mind space, then unfold. However in Whitney’s mind, tau was confined to a small space concerned in visible notion.
“One key aspect of the illness is having the tau protein unfold by way of the mind,” Llibre-Guerra says. “That was not taking place.”
The scientists set about making an attempt to know why.
They do not have a definitive reply but. However they’re intrigued by the excessive ranges of warmth shock proteins in Whitney’s mind.
These proteins assist defend mind cells from excessive temperatures and different types of stress. Additionally they appear to forestall wholesome tau from misfolding into the poisonous, phosphorylated kind related to Alzheimer’s.
“It could be the case that these proteins are stopping extra tau to be misfolded, after which unfold by way of the mind,” Llibre-Guerra says.
Safety from sizzling work?
Scientists instructed Whitney that the excessive ranges of warmth shock proteins in his mind could be the results of his life expertise.
“I spent 20 years within the Navy, most of it within the sizzling spots, just like the engine rooms of ships—110 levels is nothing on a ship,” he says.
That surroundings could have brought on a rise in warmth shock proteins, which have been capable of restrict the unfold of tau and forestall the onset of Alzheimer’s.
The scientists learning Whitney aren’t positive if that is all, and even half, of the reason. However they’re hoping that the paper on Whitney will encourage different researchers to search for solutions.
Within the meantime, Whitney plans to proceed making his mind and physique out there to scientists. Later this yr, he’ll return to Washington College in St. Louis, the place he has undergone repeated mind scans, blood attracts, lumbar punctures, and even offered a pattern of bone marrow.
Whitney’s hope is that scientists will be taught one thing that helps defend different brains from Alzheimer’s.
“I might like to see that occur,” he says, “whereas I am nonetheless round.”
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