Exploring Animal Models to Inform Treatments for Alzheimer-Related Epileptic Activity: Christos Lisgaras, PhD, MSc

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"Our research employs a pharmacological approach, and we aspire to enhance specificity. We are actively pursuing a closed-loop protocol to real-time detect and disrupt epileptiform activity, providing a highly specific method to determine its source and selectively intervene."

Research shows that there is a large overlap between Alzheimer disease (AD) and epilepsy, and patients with either of these conditions often experience seizures and have abnormalities in the same brain structures.¹ In addition, these patients often have abnormal electrical activity called interictal spikes (IIS), which researchers have observed to be associated with impaired memory, occurring in the temporal lobes of patients with AD and epilepsy. Overall, patients living with epilepsy are at high risk of developing AD, and patients living with AD are at high risk of developing epilepsy.

In preclinical data published in Neurobiology of Disease, researchers identified a hotspot for abnormal electrical activity in a normally silent area of the brain that is essential for learning and memory which could have implications for the treatment of both conditions.² The research also determined that inhibiting a single brain cell type in the medial septum that is active during REM reduces this hyperactivity without affecting sleep. These findings were also recently presented at the 2023 American Epilepsy Society Annual Meeting, held December 1-5, in Orlando, Florida, by lead author Christos Lisgaras, PhD, MSc, a research scientist at both NYU Langone Health and The Nathan S. Kline Institute for Psychiatric Research, and colleagues.³

Following the meeting, Lisgaras sat down in an interview with NeurologyLive® to further discuss the research findings. He talked about the key role that animal models, equipped with implanted electrodes, play in uncovering the source of abnormal electrical activity in AD. Lisgaras also spoke about how inhibiting the medial septum in mice models lead to a significant reduction in epileptiform activity, and the implications this holds for future treatments. In addressing the heterogeneity of AD, he explained how collaborative efforts between clinicians, basic scientists, and allied health professionals can help contribute to the development of targeted treatments.

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REFERENCES
1. Lisgaras CP, Scharfman HE. High-frequency oscillations (250-500 Hz) in animal models of Alzheimer's disease and two animal models of epilepsy. Epilepsia. 2023;64(1):231-246. doi:10.1111/epi.17462
2. Lisgaras CP, Scharfman HE. Interictal spikes in Alzheimer's disease: Preclinical evidence for dominance of the dentate gyrus and cholinergic control by the medial septum. Neurobiol Dis. 2023;187:106294. doi:10.1016/j.nbd.2023.106294
3. Early Research Pinpoints Area of the Brain Where Epileptic Activity May Occur in Some Alzheimer’s Disease Patients, Finding Could Lead to Targeted Treatments. News Release. American Epilepsy Society. Published December 1, 2023. Accessed December 7, 2023. https://aesnet.org/about/about-aes/press-room/early-research-pinpoints-area-of-the-brain-where-epileptic-activity-may-occur-in-some-alzheimer-s-disease-patients-finding-could-lead-to-targeted-treatments