Man destined to get Alzheimer’s saved by accidental heat therapy

In the United States, a man who was virtually guaranteed to contract Alzheimer’s disease at an early stage due to his genetic characteristics managed to avoid it, perhaps thanks to his accidental exposure to heat while working as a mechanic in the engine room of ships. This case is consistent with growing evidence from studies in humans and other animals that suggest heat therapy may protect against this disease.

Doug Whitney’s family carries a variant of a gene called Presenilin 2inherited from ancestors dating back to a small 18th century Volga German village. Carriers of this mutation, which causes aberrant protein folding in the brain, almost always develop Alzheimer’s disease in their late 40s or early 50s.

“My family has been devastated by this illness,” Whitney said in a press release. “My mother had 13 brothers and sisters, and 10 of them died before the age of 60. It’s a scourge.”

Despite inheriting the same mutation, Whitney reached his 60s without developing major memory problems or other symptoms of Alzheimer’s disease. To date, he is the only known carrier to have escaped this disease for many years after its expected onset.

Geoffrey Canet of the French National Center for Scientific Research became interested in Whitney’s case after having a discussion at a conference with Randall Bateman of Washington University in St. Louis, Missouri, who has studied Whitney for years.

At the conference, Canet presented his team’s research on the beneficial effects of thermotherapy on the brains of mice. Studies in Finland found that frequent sauna users are 65% less likely to develop Alzheimer’s disease than occasional sauna enthusiasts, leading Canet and his colleague Emmanuel Planel of Laval University in Quebec to study the underlying mechanisms.

Their results piqued Bateman’s interest, because he knew that Whitney had worked for two decades in the very hot engine rooms of steam warships, starting at the age of 18. Bateman discussed the case with Canet and Planel, who were inspired to investigate further.

Ships’ engine rooms can reach temperatures of 50°C (122°F) and Whitney would sometimes stay there for hours at a time, sometimes having to be hosed down to prevent overheating.

Perhaps due to this heat exposure, Whitney has unusually high levels of heat shock proteins in her spinal fluid. Our bodies produce them in response to heat to repair and refold certain other types of proteins that might be damaged by increased temperature.

These high levels of heat shock proteins may have prevented Whitney from developing Alzheimer’s disease by regulating an important brain protein called tau, Canet says. Tau becomes misfolded and aggregates into tangled clumps in people with this disease, which correlates with cognitive decline. Imaging studies have shown that Whitney’s brain contains very little of this abnormal tau protein, which likely explains her lack of symptoms. On the other hand, his brain is full of misfolded amyloid protein, also characteristic of Alzheimer’s disease, but which seems less predictive of symptoms.

Supporting their hypothesis, Canet and Planel found that placing mice in miniature saunas helped keep their tau protein structures in shape and increased their clearance from the brain. Similarly, they found that brain Tau clearance was higher in healthy older adults when they were awake rather than asleep, perhaps because body temperature is naturally higher when people are awake.

Rebecca Nisbet of the Florey Brain Research Center in Australia says Whitney’s occupational exposure to heat could be a factor in her resistance to Alzheimer’s disease, but adds that her genetics probably also play a role. For example, he was found to have certain genes that differ from those of his affected family members and may be protective. “These are genes that we know are involved in Alzheimer’s disease,” she says.

Nonetheless, Nisbet says she started using saunas herself, based on emerging evidence of their benefits for the brain. “I think it’s one of those things that won’t hurt and can reduce your risk of dementia,” she says.

Interestingly, the regions of the world with the lowest rates of cognitive impairment and Alzheimer’s disease among people over 60 tend to be very hot, including the rural town of Ballabgarh in India and the Bolivian Amazon. “Of course, high temperature probably doesn’t explain everything, but it can be a factor,” says Canet.

Conversely, exposure to cold can increase the risk of Alzheimer’s disease. For example, tau protein is known to be dysregulated in bears during their winter hibernation, Nisbet explains. “The tau in bears’ brains looks like a disease during their hibernation, but as soon as they wake up and warm up, it returns to normal,” she says.

Studies in humans have also shown that general anesthesia, which reduces body temperature, can cause short-term cognitive problems reminiscent of Alzheimer’s disease, likely due to its effect on tau protein. “We have to be careful in our studies on mice, because if you anesthetize them for too long during treatments, it can actually lead to dysregulation of the tau protein,” says Nisbet.