Exploring how Alzheimer's alters the brain's electrical activity

Postdoctoral researcher Annie Goettemoeller is studying links between epilepsy-like, subclinical hyperexcitability and the early spread of amyloid and tau in Alzheimer's, focusing on entorhinal cortex input to the dentate gyrus and using tools that can selectively modify that circuit.

Annie Goettemoeller, a Wu Tsai Neurosciences Institute postdoctoral scholar at Stanford, is investigating how Alzheimer's disease alters electrical activity in the brain and how those changes may relate to the spread of amyloid and tau pathology. She is concentrating on early circuit changes that appear before severe symptoms, notably in the entorhinal cortex and its communication with the hippocampal dentate gyrus. Her work builds on observations that some patients show epilepsy-like, subclinical electrical discharges before diagnosis and on animal studies that link hyperexcitability to spread of pathology. Collaborations at Stanford bring tools that can selectively alter specific neural connections to test whether circuit changes drive or compensate for disease. Key facts: - The research links epilepsy-like, subclinical hyperexcitability with early Alzheimer's-related changes and with the reported spread of amyloid and tau in prior studies. - The entorhinal cortex is highlighted as an early-vulnerable region; its input to the dentate gyrus includes coordinated events called dentate spikes that are implicated in memory processes. - Teams are using methods that can selectively disrupt the entorhinal-to-dentate connection in mice to observe whether such changes affect memory measures or alter the course of pathology; these experiments are ongoing. Summary: Goettemoeller's project aims to clarify whether abnormal electrical activity in the entorhinal–dentate circuit contributes to disease progression or represents an adaptive response. Near-term work will test in mouse models whether stabilizing or repairing that circuit changes cognitive outcomes; longer-term questions about how electrical activity and molecular pathology interact remain under investigation.