Lithium inhibits amyloid secretion in COS7 cells transfected with amyloid precursor protein C100

To examine the regulation of amyloid secretion in more detail, Aβ sandwich ELISAs with high sensitivity and specificity were developed. Using this technique, we measured Aβ secreted from COS7 cells transiently transfected with APP C100 in the presence of LiCl, a potent glycogen synthase kinase (GSK)-3β inhibitor. We found that both Aβx-40 and Aβx-42 secretion were reduced by LiCl treatment in a dose-dependent manner. Diminished amyloid secretion was associated with GSK-3β activity. These results suggest that GSK-3β might function as a possible mediator for regulating both amyloid deposition and tau pathology in Alzheimer's disease (AD), and that lithium should be re-evaluated as a candidate reagent for preventing AD pathology.