Imagine you’re in a taste test, trying to determine the secret ingredient that makes a dish so irresistible. You sample one plate after another, searching for that distinct flavor. Similarly, researchers injected synthetic Aβ1-42 oligomers into mice to see if it affected their susceptibility to seizures. Previous studies suggested that these oligomers, implicated in Alzheimer’s disease, could increase seizure susceptibility. However, this new study found no evidence of a connection between Aβ1-42 oligomers and seizures in mice. It seems that different batches or forms of Aβ1-42 may yield conflicting results in various experiments. While the current findings are intriguing, more research is needed to fully understand how Aβ1-42 oligomers might influence seizures in Alzheimer’s disease. To dive deeper into this fascinating study, head over to the original research article!

ObjectivesEpileptiform activity and seizures are present in patients with Alzheimer’s disease (AD) and genetic animal models of AD. Amyloid beta 1-42 (Aβ1-42) oligomers are thought to be crucial in AD and can cause neuronal hyperexcitability in vitro. However, it is unclear whether these Aβ1-42 oligomers cause the increased seizure susceptibility in vivo in people with AD and in AD animal models, nor via which mechanisms it would do so. We investigated this question by injecting Aβ1-42 oligomers intracerebrally in mice and assessed its impact on seizure susceptibility.Materials and methodsWe performed a single intracerebral injection of synthetic Aβ1-42 oligomers or scrambled Aβ1-42 in NMRI mice in three different cohorts and subjected them to an i.v. infusion of a chemoconvulsant. We evoked the seizures 1.5 h, 1 week, or 3 weeks after the intracerebral injection of Aβ1-42 oligomers, covering also the timepoints and injection locations that were used by others in similar experimental set-ups.ResultsWith a thioflavine T assay and transmission electron microscopy we confirmed that Aβ1-42 monomers spontaneously aggregated to oligomers. We did not find an effect of Aβ1-42 oligomers on susceptibility to seizures – evoked 1.5 h, 1 week or 3 weeks – after their intracerebral injection.SignificanceThe lack of effect of Aβ1-42 oligomers on seizure susceptibility in our experiments contrasts with recent findings in similar experimental set-ups. Contradicting conclusions are frequent in experiments with Aβ1-42 and they are often attributed to subtle differences in the various aggregation forms of the Aβ1-42 used in different experiments. We confirmed the presence of Aβ1-42 oligomers with state-of-the-art methods but cannot ascertain that the protein aggregates we used are identical to those used by others. Whether our findings or those previously published best represent the role of Aβ1-42 oligomers on seizures in AD remains unclear.

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