Epilepsyis a common neurological disorder, affecting50 million people worldwide，其特征是由于大脑中神经元异常而导致复发无端癫痫发作的趋势。癫痫会影响各个年龄段的人们，但有趣的是，它也与早熟的发展有关Alzheimer’s Disease(AD)-type neuropathological changes, such as the accumulation ofamyloid-β (Aβ) as senile plaquesand increased microglial activation compared to healthy individuals. AD itself mostly affects older people, with onset typically occurring from the age of 65 years.

It is known that there is a genetic predisposition to AD, so that individuals carrying two copies of theApolipoprotein E(ApoE) variant epsilon 4 have amuch higher risk of developing the diseasethan those with other variants of this gene. But why is this?

In aresearch article最近出版BMC Medicine,Sue Griffinand colleagues elucidate the mechanism behind this using a remarkably simple yet clever model. Using temporal lobe tissue removed from the brains oftemporal lobe epilepsy(TLE) patients aspart of their treatment, the research team were able to investigate the physiological effects of variousApoE基因变异对大脑组织,同时same time avoiding the confounding factors that would come with investigating these effects in AD patients’ brains. For instance, looking at tissue from younger brains meant that there were likely to be very few age-related changes.

The research team looked at different markers of neuronal injury and resilience in brain tissue derived from patients that had two copies of the episilon 4 variant and compared them to those that that two copies of the episilon 3 variant. They found that the episilon 4 variant is not only associated with an increased burden of Aβ plaques, but is also associated with a compromised ability to combat the neuronal toxicity of these plaques. In contrast, the episilon 3 variant was associated with neuroprotection, meaning that carriers of this variant are less likely to be adversely affected by AD changes.