Man destined for Alzheimer’s may have been saved by accidental therapy

A man in the US who was virtually guaranteed to get early-onset Alzheimer’s disease because of his genetics has somehow dodged it, possibly thanks to his inadvertent heat exposure while working as a mechanic in ship engine rooms. The case fits with growing evidence from studies in humans and other animals that suggest that heat therapy may protect against the condition.

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

“My family has been devastated by this disease,” Whitney said in a press statement. “My mom had 13 brothers and sisters, and 10 died before they were 60 years old. It’s been a plague.”

Despite inheriting the same mutation, Whitney has reached his late 70s without developing any major memory problems or other symptoms of Alzheimer’s disease. To date, he is the only known carrier to escape the condition for many years after its expected onset.

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

At the conference, Canet presented his team’s research on the beneficial effects of heat therapy on the brains of mice. Studies in Finland have found that frequent sauna users are 65 per cent less likely to develop Alzheimer’s disease than occasional dabblers, which led Canet and his colleague Emmanuel Planel at Laval University in Quebec to study the underlying mechanisms.

Their results piqued Bateman’s interest, since he knew Whitney had worked for two decades in the very hot engine rooms of steam-propelled navy ships, starting when he was 18. Bateman discussed the case with Canet and Planel, who were inspired to investigate it further.

Ship engine rooms can reach temperatures of 50°C (122°F) and Whitney was sometimes in them for hours at a time, occasionally having to be hosed down to avoid overheating.

Possibly as a result of this heat exposure, Whitney has unusually high levels of heat shock proteins in his cerebrospinal fluid. Our bodies produce these in response to heat to repair and refold certain other types of proteins that might be damaged by the 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, says Canet. Tau becomes misfolded and aggregates in tangled clumps in people with the condition, which correlates with cognitive decline. Imaging studies have found that Whitney’s brain contains very little of this abnormal tau, which probably explains his lack of symptoms. On the other hand, his brain is full of misfolded amyloid protein, which is also characteristic of Alzheimer’s disease, but appears to be less predictive of symptoms.

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

Rebecca Nisbet at The Florey brain research centre in Australia says that Whitney’s occupational heat exposure could be one factor explaining his resistance to Alzheimer’s disease, but adds that his genetics probably also play a role. For example, he has been found to have certain genes that differ from those of his affected family members and may be protective. “They’re genes that we know are involved in Alzheimer’s disease,” she says.

Nevertheless, Nisbet says she has started using saunas herself based on the emerging evidence of their brain benefits. “I think it’s one of those things that isn’t going to hurt and may reduce your dementia risk,” she says.

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

Conversely, cold exposure may increase the risk of Alzheimer’s disease. For example, tau is known to become dysregulated in bears during their winter hibernation, says Nisbet. “The tau in the bears’ brains looks disease-like while they’re hibernating, but as soon as they wake up and warm up again, it somehow goes back to looking normal,” she says.

Studies in people have also found that general anaesthesia, which reduces body temperature, can cause short-term cognitive problems that are reminiscent of Alzheimer’s, possibly because of its effect on tau. “We have to be careful in our mouse studies because if you anaesthetise them for too long during treatments, it can actually drive dysregulation of tau,” says Nisbet.