A Comparative Study of β-Amyloid Peptides Aβ1-42 and Aβ25-35 Toxicity in Organotypic Hippocampal Slice Cultures

Accumulation of the neurotoxic amyloid beta-peptide (A beta) in the brain is a hallmark of Alzheimer's disease (AD). Several synthetic A beta peptides have been used to study the mechanisms of toxicity. Here, we sought to establish comparability between two commonly used A beta peptides A beta 1-42 and A beta 25-35 on an in vitro model of A beta toxicity. For this purpose we used organotypic slice cultures of rat hippocampus and observed that both A beta peptides caused similar toxic effects regarding to propidium iodide uptake and caspase-3 activation. In addition, we also did not observe any effect of both peptides on Akt and PTEN phosphorylation; otherwise the phosphorylation of GSK-3 beta was increased. Although further studies are necessary for understanding mechanisms underlying A beta peptide toxicity, our results provide strong evidence that A beta 1-42 and the A beta 25-35 peptides induce neural injury in a similar pattern and that A beta 25-35 is a convenient tool for the investigation of neurotoxic mechanisms involved in AD.