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Getting the latest healthcare news for you
Getting the latest healthcare news for you
A cancer mutation found in the blood of most people over 70 is at the center of a scientific debate: does it protect against Alzheimer's disease or drive it? Two research groups studied the same mutations in the same brain cells and reached opposite conclusions — and the answer may hinge on which gene is mutated and when in the disease process you look.
Clonal hematopoiesis of indeterminate potential (CHIP) — a condition where mutant white blood cell clones accumulate with age — affects 10%–30% of people by age 70. While CHIP is known to raise leukemia and atherosclerosis risk, two research groups recently clashed over what happens when these mutant cells reach the brain.
A Stanford-led team found that CHIP carriers were 36% less likely to develop Alzheimer's dementia, with postmortem brain tissue showing CHIP mutations colonizing up to 95% of microglia. A Harvard-led team, using deeper sequencing on 190 Alzheimer's and 121 control brains, found the opposite: Alzheimer's brains harbored more CHIP mutations, concentrated in microglia locked in an inflammatory, disease-associated state. The key difference? The Harvard team could detect tiny clones the Stanford team's methods missed — and those small clones flipped the risk signal.
A third researcher at Baylor College of Medicine offered a reconciling view: the effect may be gene-specific and timing-dependent. TET2 mutations (but not DNMT3A) were linked to a 47% lower risk of late-onset Alzheimer's in a 450,000-person UK Biobank study, possibly by enhancing amyloid clearance early in disease — while later, the same inflammatory response may become harmful.
Key Takeaways:
Why it matters: With no curative treatments for Alzheimer's, understanding how bone-marrow-derived immune cells shape neurodegeneration could open entirely new therapeutic avenues. But the field first needs to resolve whether these mutations are friend, foe, or both.
