A Man Destined for Alzheimer’s Defied It for Decades—Here’s How

In a remarkable case, a man with a high genetic risk for Alzheimer’s defied the odds, avoiding the disease for decades despite carrying a mutation that almost always triggers early onset. His case, the only known instance involving the PSEN2 mutation, adds to just two other recorded cases of extreme Alzheimer’s resilience—both linked to a different genetic variant.

Typically, those with the PSEN2 mutation develop Alzheimer’s around age 50. Yet, despite his brain being packed with amyloid-beta plaques—the sticky protein clusters linked to neurodegeneration—this man showed no cognitive decline. Researchers, who have tracked Alzheimer’s in his family since 2011, found that his mother and 11 of her 13 siblings all carried the same mutation and were diagnosed by 50.

Determined to uncover what protected him, scientists studied his case in hopes of identifying broader mechanisms behind the disease. In all forms of Alzheimer’s, amyloid plaques gradually accumulate until they trigger widespread tau protein tangles, neuron death, and cognitive decline. However, over a decade of monitoring, led by researchers from the International University of Catalonia and Washington University in St. Louis, the man’s cognitive tests remained normal.

A Unique Case: Resistance Without Known Protective Mutations

Unlike previous Alzheimer’s-resistant cases, he lacked protective mutations. Yet, despite heavy amyloid buildup by age 61, his brain showed minimal inflammation, and tau deposits remained confined to the occipital lobe, preserving cognitive function.

Researchers note that limiting tau spread may be key to delaying symptoms, even with high amyloid levels. His resistance likely stems from genetic and environmental factors—he carried nine unique variants affecting brain inflammation and protein folding. Years of extreme heat exposure as a navy ship mechanic may have also activated protective cellular responses.

Studying how his brain contained tau spread could reveal new Alzheimer’s treatments.

Read Original Article: Science Alert

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