Roughly 5% of all cases of Alzheimer’s disease (AD) are caused by genetic variants in three genes, causing autosomal dominant early-onset Alzheimer’s disease. Duplications in the amyloid precursor protein (APP) gene, and variants in presenilin 1 and presenilin 2 (PSEN 1 and PSEN2) cause AD nearly 100% of the time. There is also an increased likelihood that early-onset AD patients will experience comorbid seizures more frequently than similarly-aged healthy adults. Whether these seizure affect the trajectory of disease is also less clear.

We are currently applying our expertise in preclinical models of seizure and epilepsy to better understand why and how seizures arise in the setting of early-onset AD. We are also very interested in understanding whether these seizures are differentially controlled by common anticonvulsant drugs so that treatment of clinical seizures in people with AD may be one day better controlled.

Our recent paper in Neurobiology of Disease highlights our innovative work to use the very common mouse corneal kindling model to evaluate the rate of chronic seizure development in mice with and without loss of the presenilin 2 gene. The key findings of this manuscript suggest that loss of normal PSEN2 function can actually lead to a slowed acquisition of the kindled state, e.g. epilepsy. However, there was no remarkable difference in anticonvulsant drug efficacy in mice with PSEN2 loss. From a clinical perspective, it could suggest that anticonvulsant drugs can control seizures as effectively in patients with AD as in healthy elderly adults with seizures.