B vitamin deficiency promotes pathological markers for Alzheimer's disease. - GreenMedInfo Summary
B vitamin deficiency promotes tau phosphorylation through regulation of GSK3beta and PP2A.
J Alzheimers Dis. 2010 Jan 1;19(3):895-907. PMID: 20157245
Department of Surgery "P. Valdoni", Sapienza University of Rome, Rome, Italy Center for Research in Neurobiology "Daniel Bovet", Sapienza University of Rome, Rome, Italy.
Neurofibrillary tangles (NFTs), composed of intracellular filamentous aggregates of hyperphosphorylated protein tau, are one of the pathological hallmarks of Alzheimer's disease (AD). Tau phosphorylation is regulated by the equilibrium between activities of its protein kinases and phosphatases; unbalance of these activities is proposed to be a reasonable causative factor to the disease process. Glycogen synthase kinase 3beta (GSK3beta) is one of the most important protein kinase in regulating tau phosphorylation; overexpression of active GSK3beta causes ADlike hyperphosphorylation of tau. Protein phosphatase 2A (PP2A) is the major phosphatase that dephosphorylates tau; it was demonstrated that highly conserved carboxyl-terminal sequence of PP2A C-subunit is a focal point for phosphatase regulation. This is the site of a reversible methyl esterification reaction that controls AB