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N-homocysteinylation of tau and MAP1 is increased in autopsy specimens of Alzheimer’s disease and vascular dementia

Journal of Pathology Feb 18, 2019

Bossenmeyer-Pourié C, et al. – In this study, researchers assessed the homocysteinylation of microtubule-associated proteins (MAPs) in the brains of patients with Alzheimer’s disease or vascular dementia, and in rats depleted in folate and vitamin B12, Cd320 KO mice with selective B12 brain deficiency and H19-7 neuroprogenitors lacking folate. In rats exposed to vitamin B12 and folate deficiency during gestation and lactation, N-homocysteinylation increased and remained significantly higher when they were 450 days old, despite their return to normal diet at weaning, compared with controls. Investigators found that increased N-homocysteinylation of tau and MAP1 is a brain ageing mechanism that is dependent upon the concentration of homocysteine and Methionine tRNAsynthetase enzyme. Its lifelong irreversibility and cumulative occurrence may explain why B12 and elderly folate supplementation have such a narrow impact on preventative brain ageing and cognitive decline.

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