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The amyloid β‐peptides have been implicated in the excitotoxic mechanism of neuronal injury in the pathogenesis of Alzheimer's disease. In this paper we examine the effect of different amyloid fragments (β A1–40, A1–28, and A25–35), as well as potential neuroprotective compounds on rat cortical neuron viability. Exposure of neurones to β A25–35 or A1–40 at concentrations as low as 1 μg/ml inhibited, significantly, the MTT response and this level of inhibition was similar after 24‐h or three‐day exposure. Furthermore, the level of inhibition was not affected by the presence or absence of 5% horse serum in the medium. Preexposure (10 min) of neurones to ALC at concentrations of 0.1, 1, 5, and 10 mM attenuated the inhibition of the MTT response caused by β A25–35 (50 μg/ml) in serum free medium for 24 h. The treatment of cells with vitamin E (100 μM), catalase (4 mg/ml), NGF (0.1 and 10 ng/ml), or cycloheximide (0.1 μg/ml) significantly restored the MTT response that was inhibited by β A25–35. The mechanism for the protective actions of these compounds against β A25–35 toxicity is not clear but may involve free radical scavenger action and preservation of energy production, although other mechanisms, especially for ALC, such as a direct effect on A‐β interaction with charged anionic phospholipids and/or stabilizing action on membranes, are also possible.

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