• β-Amyloid;
  • Neurotoxicity;
  • Calcium;
  • Nimodipine;
  • Cell culture;
  • Alzheimer's disease.

Abstract: Deposit of β-amyloid protein (Aβ) in Alzheimer's disease brain may contribute to the associated neurodegeneration. We have studied the neurotoxicity of Aβ in primary cultures of murine cortical neurons, with the aim of identifying pharmacologic ways of attenuating the injury. Exposure of cultures to Aβ (25–35 fragment; 3–25 4mUM) generally triggers slow, concentration-dependent neurodegeneration (over 24–72 h). With submaximal Aβ- (25–35) exposure (10 μM), substantial (>40% within 48 h) degeneration often occurs and is markedly attenuated by the presence of the Ca2+ channel blockers nimodipine (1–20 μM) and Co2+ (100 μM) during the Aβ exposure. However, Aβ neurotoxicity is not affected by the presence of glutamate receptor antagonists. We suggest that Ca2+ influx through voltage-gated Ca2+ channels may contribute to Aβ-induced neuronal injury and that nimodipine and Co2+, by attenuating such influx, are able to attenuate Aβ neurotoxicity.