Different fibrillar Aβ 1-42 concentrations induce adult hippocampal neurons to reenter various phases of the cell cycle

In Alzheimer's disease (AD) cell cycle reentry precedes neuronal death, which could be induced by many cytotoxic factors. It is believed that beta amyloid (AD), the major component ofextracellular plaques in AD, is potent in inducingneurons to reenter cell cycle. In AD brains, neurons expressing cell cycle markers are reported in many brain regions without any plaque formation, although very low levels of A beta may still be detected. In the other side, because cell cycle reentry is not an immediate cause of apoptosis, neurons may remain in cell cycle phases forsome time prior to their final death. Inthis studywe examined if very low concentrations of A beta 1-42 (picomolar) can trigger the adult neurons to reenter the cell cycle, and the effect of different A concentrations on neuronal progression through differentcell cycle phases. Primary adult neurons were treatedwithA beta 1-42 at 2x 10(-6),2 x 10(-5), 2 x 10(-4), 0.5 and 2.5 pM concentrations. Cyclin Di and cyclin B1 (the markers for G1 and G2 phases of the cell cycle, respectively) and apoptosis were assessed. Treatment with Af at 2.5 mu M induced apoptosis. At lower levels however, A beta promoted neurons entering G1 and G2 phases without apoptosis, with 0.5 pM of A beta inducing neurons into G2, and 2 x 10(-5), 2 x 10(-4) into G1 phases. Our results suggested that lower concentrations of Af induced neurons to reenter the cell cycle, and different concentrations had differential abilities to promote neurons into various cell cycle phases or trigger their death. (c) 2008 Elsevier B.V. All rights reserved.