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Loss of NRF2 in myelin‑making cells linked to faster cognitive decline In a study published Nature Medicine, August 25, researchers linked loss of the protective protein NRF2 in oligodendrocytes to faster cognitive decline in humans, matching long‑term cognitive testing with post‑mortem white‑matter analysis. Participants from a British cohort took an IQ test at age 11; from ages 70–82 they were tested roughly every three years on memory, processing speed and visuospatial ability. After death, the corpus callosum was examined; those with faster decline showed less compact myelin, thinner axons with relatively thicker sheaths, more oligodendrocytes and a lower proportion of NRF2‑positive cells. At six months, scientists knocked out NRF2 only in mature oligodendrocytes; by twelve months, mutant males improved their performance in a four‑day water‑maze task by 27.82%, whereas controls improved by 57.75%. In a separate group of 18‑month mice with the same knockout in the corpus callosum, axons were thinner and myelin sheaths relatively thicker. These changes mirrored the human pattern, indicating that NRF2 loss in myelin‑producing cells drives white‑matter alterations associated with age‑related cognitive slowing. 🔗 Read original →