Lithium protects cultured neurons against β-amyloid-induced neurodegeneration

The deposition of β-amyloid peptide (Aβ), the hyperphosphorylation of tau protein and the death of neurons in certain brain regions are characteristic features of Alzheimer's disease. It has been proposed that the accumulation of aggregates of Aβ is the trigger of neurodegeneration in this disease. In support of this view, several studies have demonstrated that the treatment of cultured neurons with Aβ leads to the hyperphosphorylation of tau protein and neuronal cell death. Here we report that lithium prevents the enhanced phosphorylation of tau protein at the sites recognized by antibodies Tau-1 and PHF-1 which occurs when cultured rat cortical neurons are incubated with Aβ. Interestingly, lithium also significantly protects cultured neurons from Aβ-induced cell death. These results raise the possibility of using chronic lithium treatment for the therapy of Alzheimer's disease.This research was supported by grants from the Spanish Direccion General de Investigacion Cientifica y Tecnica (PB 94-0040 and PM 95-0039) and an institutional grant to the Centro de Biologia Molecular `Severo Ochoa' from the Fundacion Ramon Areces. G.A. is the recipient of a fellowship from the Ministerio de Educacion y Cultura.Peer reviewe