Bossenmeyer-Pourié C, et al. - In this investigation, researchers examined the homocysteinylation of microtubule-associated proteins (MAPs) in the brains of Alzheimer’s disease or vascular dementia patients, in rats depleted in folate and vitamin B12, Cd320 KO mice with selective B12 brain deficiency, and H19-7 neuroprogenitors lacking folate. Investigators found that N-homocysteinylation increased during gestation and lactation in rats exposed to vitamin B12 and folate deficiency and stayed significantly higher at 450 days of age, even after returning to a normal weaning diet vs controls. They observed that increased N-homocysteinylation of tau and MAP1 is a brain ageing mechanism dependent upon homocysteine concentration and methionine tRNAsynthetase (MARS) enzyme expression. Its lifelong irreversibility and cumulative occurrence might explain why B12 and folate supplementation for the elderly have a low, if any, effect in the prevention of pathological brain ageing and cognitive decline.