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AAIC 2022 | What drives network hyperexcitability in Alzheimer’s disease?

Sean Tok, PhD Candidate, Janssen Inc., Beerse, Belgium, shares an overview of what we know about the mechanisms underlying the presence of neuronal network hyperexcitability in Alzheimer’s disease (AD). The exact mechanisms causing neuronal excitability changes are not fully characterized; however, pathological amyloid β (Aβ) is thought to be a contributing factor. Several studies have shown that Aβ can provoke changes in neuronal activity. Aβ has been hypothesized to contribute by decreasing the uptake of glutamate and increasing extrasynaptic NMDAR activation, reducing the expression of Kv4 channels, and perturbing Ca2+ homeostasis. However, these hypotheses have been built on animal models with limitations, in which protein overexpression may be exacerbating the network hyperexcitability seen. Mr Tok emphasizes the importance of examining hyperexcitability in newer models in order to get a clearer picture of its relationship with AD pathology. This interview took place at the Alzheimer’s Association International Conference (AAIC) 2022 in San Diego, CA.


Sean Tok reports the following disclosures: Janssen Pharmaceuticals