Abstract: β‐Amyloid is a metabolic product of the amyloid precursor protein, which accumulates abnormally in senile plaques in the brains of patients with Alzheimer's disease. The neurotoxicity of 0‐amyloid has been observed in cell culture and in vivo, but the mechanism of this effect is unclear. In this report, we describe the direct neurotoxicity of β‐amyloid in high‐density primary cultures of human fetal cortex. In 36‐day‐old cortical cultures, β‐amyloid neurotoxicity was not inhibited by the broad‐spectrum excitatory amino acid receptor antagonist kynurenate or the NMDA receptor antagonist D‐2‐amino‐5‐phosphonovaleric acid under conditions that inhibited glutamate and NMDA neurotoxicity. In 8‐day‐old cortical cultures, neurons were resistant to glutamate and NMDA toxicity but were still susceptible to β‐amyloid neurotoxicity, which was unaffected by excitatory amino acid receptor antagonists. Treatment with β‐amyloid caused chronic neurodegenera‐tive changes, including neuronal clumping and dystrophic neurites, whereas glutamate treatment caused rapid neuronal swelling and neurite fragmentation. These results suggest that β‐amyloid is directly neurotoxic to primary human cortical neurons by a mechanism that does not involve excitatory amino acid receptors.

Busciglio, J., Yeh, J., & Yankner, B. A. (1993). β‐Amyloid Neurotoxicity in Human Cortical Culture Is Not Mediated by Excitotoxins. Journal of Neurochemistry, 61(4), 1565–1568. Portico.