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FEBS Lett. 2002 May 8;518(1-3):1-4.

Protein phosphatase 2A methylation: a link between elevated plasma homocysteine and Alzheimer's Disease.

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  • 1Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.


Tau hyperphosphorylation is a central event in the development of Alzheimer's Disease (AD). Protein phosphatase 2A (PP2A) heterotrimer formation is necessary for efficient dephosphorylation of the tau protein. S-Adenosylmethionine-dependent carboxyl methylation is essential for the assembly of PP2A heterotrimers. Epidemiological evidence indicates that elevated plasma homocysteine is an independent risk factor for AD. Homocysteine is a key intermediate in the methyl cycle and elevated plasma homocysteine results in a global decrease in cellular methylation. We propose that the PP2A methylation system is the link relating elevated plasma homocysteine to AD.

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