A 75-year-old man genetically fated to develop Alzheimer’s is yet to show any sign of the disease, likely due to his lifelong exposure to high levels of heat while working as a naval mechanic, a study suggests.
Doug Whitney inherited a rare genetic mutation that caused many members of his family to develop cognitive decline in their early 50s.
But Mr Whitney remains mentally sharp. The likely reason, the study notes, is his exposure to high temperatures while working as a mechanic in the engine rooms of ships.
People who inherit Alzheimer’s genes typically experience cognitive decline at an early age, sometimes as soon as in their 30s or 40s.
But a tiny number, known as “exceptional resilience mutation carriers”, escape the condition. Scientists now say they may be key to developing treatments for Alzheimer’s. Mr Whitney is only one of the three such people known so far.
“When he came to Washington University School of Medicine for the first time, together with his cousin, he was 10 years past the age of onset for his family,” said neurologist Jorge Llibre-Guerra, author of the study published in the Journal of Alzheimer’s Disease.
“It came as a big surprise to learn that he was actually a mutation carrier.”
Mr Whitney carries a mutant form of the PSEN2 gene, which the researchers say is responsible for early-onset Alzheimer’s in every other member of his family.
“It’s really important to me to figure this out,” Mr Whitney said. “My mom had 13 brothers and sisters and 10 died before they were 60 years old. It’s been a plague.”
The PSEN2 mutation is linked to an overproduction of amyloid protein, which accumulates in the brain and contributes to the progression of Alzheimer’s.
In the disease’s second stage, associated with cognitive decline, there’s usually a build-up of what’s known as the tau protein in the brain.
Mr Whitney’s body, for unknown reasons, is preventing his PSEN2 mutation from fully taking hold.
“If we can uncover the mechanism behind this resilience, we could try to replicate it with a targeted therapy designed to delay or prevent the onset of Alzheimer’s,” Dr Llibre-Guerra said.
-and-his-wife-work-on-word-puzzles-in-their-home-near-Seattle.png)
Scans of Mr Whitney’s brain show a significant accumulation of amyloid protein, but only a localised concentration of tau in one area.
His brain fluid also shows a significantly higher-than-normal level of what are known as “heat shock” proteins.
These proteins are produced by cells in response to exposure to stressful conditions like high heat or UV light and are known to act as chaperones that stabilise, fold, and repair other proteins.
“We don’t yet understand how or if heat shock proteins may be mediating the effect,” Dr Llibre-Guerra said.
“However, in this case, they may be involved in preventing aggregation and misfolding of tau proteins.”
The researchers suspect Mr Whitney’s work as a shipboard mechanic may have left him with elevated levels of heat shock proteins.
“We highlight evidence from preclinical, clinical, and epidemiological studies suggesting that elevated body temperature promotes tau clearance,” they wrote in the study.
“This observation invites deeper investigation into thermo-regulation as a modifiable factor in tau homeostasis and Alzheimer’s disease vulnerability, with implications for both biomarker interpretation and therapeutic strategies.”