Alzheimer’s disease (AD) is a devastating neurodegenerative disease that affects over 4 million people in the US alone. As the worldwide population continues to age, this number will only grow in the coming decades. Seizures in people with both early- and late-onset AD are more common than in similarly age-matched non-affected individuals. People with epilepsy have significant cognitive decline if seizures are left uncontrolled. Uncontrolled seizures in AD may similarly worsen cognitive function. However, it is relatively unclear whether these seizures are a cause of cognitive decline in AD, or whether they are just a byproduct of pathological remodeling due to AD itself.

We are actively determining whether commonly available antiseizure medicines (ASMs) can be differentially effective against evoked focal seizures in a diversity of rodent AD models. Our recent study “Higher susceptibility to 6 Hz corneal kindling and lower responsiveness to antiseizure drugs in mouse models of Alzheimer’s disease” in collaboration with the Smolders lab at Vrije Universiteit Brussel adds to this growing body of evidence to suggest that ASMs would benefit people with AD. However, these ASMs may be differentially beneficial in discrete AD genotypes, highlighting a precision medicine strategy for seizures in AD. In this recent study, we show that two distinct AD models – 3xFAD and APP/PS1 mice – have vastly increased susceptibility to evoked seizures. This is starkly in contrast to our 2020 work in a mouse model with loss of normal presenilin 2 (PSEN2) function, in which PSEN2 null mice exhibited significant age-related delays in kindling rate. We altogether find substantial genotype specific differences in susceptibility to kindling with AD genotypes.

How ASMs may control seizures in AD still requires much greater investigation. It is possible there could be a strategy for rational drug selection to control seizures in AD. This recent study and our earlier investigations suggest that selected ASMs may be better for certain AD genotypes, but more work in aged animals is clearly needed.