Tangle formation and tau phosphorylation

Tangles are composed of paired helical filaments, themselves composed of hyperphosphorylated tau. It is not fully determined whether tau phosphorylation precedes tau aggregation, but tau is highly phosphorylated in fetal brain and, albeit to a lesser extent, in normal adult brain. (37) However, neuropathological evidence suggests that highly phosphorylated tau does begin to accumulate in the brain before the formation of tangles, and before the clinical manifestation of AD. (56) It seems as though, if not the only event in paired helical-filament formation, increased tau phosphorylation is at least an early event.

Protein phosphorylation is a product of kinase and phosphatase activity. It is likely that many such enzymes may participate in the regulation of tau phosphorylation in the brain, but two have been shown to be predominant. In cells, and in vitro, glycogen synthase kinase-3 is the main tau-kinase and protein phosphatase 2A is the predominant tau phosphatase/57,58*

Break Free From Passive Aggression

Break Free From Passive Aggression

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