Disruption of the cytoskeleton in Alzheimer's disease

Abstract

Paired helical filaments (PHFs) in Alzheimer's disease are formed from hyperphosphorylated brain tau known as PHF—tau. Many sites of phosphorylation that were thought to be present only in PHF—tau are now known to be normal phosphate acceptor sites in both fetal and rapidly processed adult brain tau. The rapid dephosphorylation of normal brain tau by protein phosphatases 2A and 2B provides an explanation for the apparent absence of phosphates at these sites in the normal adult brain tau obtained postmortem. Although the functional significance of each of these normal phosphate acceptor sites is unknown at this time, emerging evidence suggests that the binding of tau to microtubules is regulated by the simultaneous phosphorylation and dephosphorylation of tau at multiple sites.