Ione and Doug Whitney, February, 2025.
Megan Farmer, WashU Medication
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Megan Farmer, WashU Medication
Individuals who inherit one very uncommon gene mutation are just about assured to develop Alzheimer’s earlier than they flip 50.
Apart from Doug Whitney.
“I am 75 years outdated, and I feel I am functioning pretty properly,” says Whitney, who lives close to Seattle. “I am nonetheless not displaying any of the signs of Alzheimer’s.”
Now a staff of scientists is making an attempt to know how Whitney’s mind has defied his genetic future.
“If we’re capable of study what’s inflicting the safety right here, then we might translate that to therapeutic approaches and apply that to the extra frequent types of the illness,” says Dr. Jorge Llibre-Guerra, an assistant professor of neurology at Washington College Faculty of Medication in St. Louis.
One risk is excessive ranges of warmth shock proteins present in Whitney’s mind, the staff experiences within the journal Nature Medication.
There are hints that these proteins can stop the unfold of a poisonous protein that is without doubt one of the hallmarks of Alzheimer’s, Llibre-Guerra says.
A genetic shock
Early-onset Alzheimer’s is in every single 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 keep in mind the pumpkin pie recipe,” she says. “A 12 months later after we went again, she was already wandering off and never discovering her means again residence.”
The affected members of the family 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 needed to assist others. So he volunteered for a examine of households with early Alzheimer’s.
“I submitted my blood samples and to my nice shock, it got here again optimistic for the Alzheimer’s gene,” Whitney says. “It was fairly a shock.”
It was additionally a shock for scientists. Whitney was solely the third individual recognized to have escaped the results of a presenilin mutation.
The primary two got here from a bunch in Colombia with mutations to the presenilin 1 gene. Whitney is the one individual recognized to have resisted a mutation within the presenilin 2 gene, which is discovered on a unique chromosome.
All three had numerous 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 factor of the illness is having the tau protein unfold by the mind,” Llibre-Guerra says. “That was not occurring.”
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 shield mind cells from excessive temperatures and different types of stress. Additionally they appear to stop 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 the mind,” Llibre-Guerra says.
Safety from scorching work?
Scientists instructed Whitney that the excessive ranges of warmth shock proteins in his mind is perhaps the results of his life expertise.
“I spent 20 years within the Navy, most of it within the scorching spots, just like the engine rooms of ships—110 levels is nothing on a ship,” he says.
That surroundings could have precipitated a rise in warmth shock proteins, which had been capable of restrict the unfold of tau and stop the onset of Alzheimer’s.
The scientists finding out Whitney aren’t certain 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 obtainable to scientists. Later this 12 months, he’ll return to Washington College in St. Louis, the place he has undergone repeated mind scans, blood attracts, lumbar punctures, and even supplied a pattern of bone marrow.
Whitney’s hope is that scientists will study one thing that helps shield different brains from Alzheimer’s.
“I might like to see that occur,” he says, “whereas I am nonetheless round.”
