Man With Rare Presenilin 2 Mutation Reaches Late 70s Without Alzheimer’s Despite Expected Onset in 40s or 50s

Doug Whitney has reached his late 70s without developing any major memory problems or other symptoms of Alzheimer’s disease despite carrying a Presenilin 2 gene mutation that almost always triggers the condition in carriers’ late 40s or early 50s. Whitney is the only known carrier of the Presenilin 2 mutation to escape the condition for many years after its expected onset.

The mutation, inherited from ancestors traced to a small 18th-century Volga German village, causes aberrant folding of proteins in the brain.

His mother had 13 brothers and sisters, and 10 of them died before they were 60 years old. “My family has been devastated by this disease.

It’s been a plague,” Whitney said. A photograph of Doug Whitney with his son Brian was taken in November 2022. Whitney had a PET scan in March 2025 as part of an annual Alzheimer’s Disease research testing programme at Washington University in St.

Louis, Missouri. Imaging studies have found that Whitney’s brain contains very little abnormal tau even though his brain is full of misfolded amyloid protein. Randall Bateman at Washington University in St.

Louis, Missouri, has been studying Doug Whitney for years. Geoffrey Canet at the French National Centre for Scientific Research became interested in the case after discussions at a conference with Bateman. Canet presented research on the beneficial effects of heat therapy on the brains of mice at the conference.

Whitney worked for two decades in the engine rooms of steam-propelled navy ships, starting when he was 18. Ship engine rooms can reach temperatures of 50°C (122°F). He was sometimes in engine rooms for hours at a time and occasionally had 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. These proteins help repair and refold other proteins damaged by increased temperature. Canet said the elevated heat shock proteins may have regulated tau, keeping its structures in shape and preventing the tangled clumps that correlate with cognitive decline.

Studies in Finland found that frequent sauna users are 65 per cent less likely to develop Alzheimer’s disease than occasional users. Putting mice in miniature saunas helped keep their tau protein structures in shape and increased their elimination from the brain, according to research by Canet and Emmanuel Planel at Laval University in Quebec.

Tau clearance from the brain was greater in healthy older people when they were awake rather than asleep, the same researchers found.

1177/13872877261433226. @NewScientist reported that parts of the world with the lowest measured rates of cognitive impairment and Alzheimer’s disease in people over 60 include the rural town of Ballabgarh in India and the Bolivian Amazon, regions that tend to be very hot.

Rebecca Nisbet at The Florey brain research centre in Australia said Whitney’s occupational heat exposure could be one factor explaining his resistance but added that his genetics probably also play a role.

Whitney has 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 said. Tau becomes dysregulated in bears during their winter hibernation, Nisbet noted.

General anaesthesia, which reduces body temperature, can cause short-term cognitive problems reminiscent of Alzheimer’s. Nisbet has started using saunas herself based on emerging evidence of brain benefits. @NewScientist reported that Whitney’s case fits with growing evidence from studies in humans and other animals suggesting heat therapy may protect against the condition.