Similarly, reported that dissociated neurons maintained in cultures are resistant to Ab toxicity during the first days in culture and that Ab neurotoxicity increases with the age of the culture. This may indicate that cultured cells and cells that are embedded in the intact hippocampal synaptic circuitry and anatomy differ regarding cell properties which are crucial for Ab toxicity or that the interaction between the neural elements in the relatively intact tissue enables a counteracting protective mechanism. Evofosfamide CYP17 inhibitor Possible mechanisms may be alterations in the membrane lipid composition or an altered accessibility of lipid rafts for Ab. Similar reasons may account for the Ab effects in studies where OHCs were cultured for several weeks. These findings do not reflect the Ponatinib situation in adult tissue as we and others did not observe a fast toxic effect of Ab after in vivo application. Also consistent with our results Geula et al. did not observe a significant Ab toxicity in aged rats but found age-dependent Ab toxicity in aged monkeys. This does not exclude that the hippocampal neurons in OHCs, acutely isolated slices and in vivo are physiologically impaired, as LTP was disturbed in the acutely isolated slice preparations at least after Ab oligomer application. Recent studies increasingly indicated that soluble, pre-fibrillar Ab assemblies rather than mature fibrils may induce early neuronal alterations, leading to physiological interruption before cell death is detectable. Our LTP experiments elucidated the effects of distinct Ab species on synaptic potentiation. We show that Ab oligomers disturbed LTP, whereas Ab fibrils did not impair LTP, although Ab fibrils where higher concentrated and permanently exposed to the slices. This is in good agreement with the current view that Ab oligomers are responsible for the early disturbance of brain physiology. Whether or not LTP disturbances are a first sign of neuronal degeneration remains to be elucidated. If so, the MTT assay would evidently be unable to detect such early alterations in cellular physiology, as we demonstrated that Ab oligomer mediated LTP disruption was not reflected by MTT reduction in slices. On the other hand, studies utilizing primary neuronal and astroglial cultures showed an inhibition of MTT reduction already 2 h after Ab application. This may not necessarily reflect cell death, as Ab-induced alterations in MTT reduction in human cortical cultures could not be confirmed with other cytotoxicity assays like LDH and alamarBlue. Ab did not affect LTP in the present study, although a diminution in LTP was found by others. One possible explanation for this discrepancy is the strain dependence of the Ab effect, as Gengler showed that the influence of Ab on LTP in rat depends on their genetic background.