Time course of the effects of 5 μM Aβ1–42, 4 mM ketones, or the combination on the survival of hippocampal neurons in culture. ●, The mean control cell number/mm2 with error bar indicating the SEM where n = 12. All statistical tests performed were Mann–Whitney U tests, and significance was taken to be P < 0.05. ○, The mean cell number after exposure to Aβ1–42; ▴ after exposure to 5 μM Aβ1–42 + 4 mM d-β-hydroxybutyrate and ▵ after exposure to 4 mM d-β-hydroxybutyrate alone. Exposure to 5 μM Aβ1–42 significantly decreased the cell number compared with controls at 8 and 14 h as indicated by #. Addition of 4 mM d-β-hydroxybutyrate to cells exposed to 5 μM Aβ1–42 increased the cell number compared with exposure of Aβ1–42 alone at 8, 14, and 36 h as indicated by *. Addition of ketone bodies alone increased the cell number compared with controls as indicated by +. Our study therefore confirms the previous reports of the toxicity of Aβ1–42 to cultured hippocampal neurons (28). In addition we show that ketones not only reverse the toxicity of Aβ1–42, but act as a growth factor for neurons in culture.