Sean Tok, PhD Candidate, Janssen Inc., Beerse, Belgium, explains his work looking at the translational validity of hyperexcitability seen in animal models of Alzheimer’s disease. Neuronal network hyperexcitability is a key component of Alzheimer’s disease, manifesting as hippocampal hyperactivity, cortical hyperexcitability, and increased seizure risk. However, it is unclear if current widely used animal models accurately reflect the hyperexcitability seen in human disease. Amyloid APP-KI and APP/PS1 mice were studied to investigate this. At baseline, hyperexcitability (as indicated by increased broadband power spectra) was noted in APP/PS1 but not APP-KI animals. These data suggest that protein overexpression in the APP/PS1 animals may be contributing to an artificial presentation of neuronal network hyperexcitability. Developing a new model that mimics the alterations in neuronal circuits seen in human disease, in the complex content of amyloid/tau pathology and neuroinflammation, is an important next step. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.
