Electrophysiology of AMPA receptors in individuals resilient to Alzheimer’s disease Neuropathology

Berenice A Gutierrez, Steven Widen, William Russell, C. Dirk Keene, Agenor Limon

Research output: Contribution to conferencePoster


Alzheimer's disease (AD) is a prevalent form of dementia characterized by the accumulation of amyloid beta and pTau proteins in the brain. While clinical observations are typically used for AD diagnosis, postmortem studies have revealed individuals without dementia symptoms but with high AD pathology, referred to as resilient individuals. Calcium permeable AMPA receptors (CP-AMPARs) have been implicated in the calcium dyshomeostasis of AD, but their presence and electrophysiological response in resilient individuals remain unknown. To address this, we analyzed proteomic and transcriptomic data from a cohort of 30 individuals, including resistant (3M,4F; non-demented/no neuropathology), AD match resistant (2M, 5F; age-matched AD individuals), resilient (2M, 6F; non-demented with AD neuropathology), and AD match resilient (2M, 5F; age-matched AD individuals). Our analysis demonstrated alterations in the expression, organization, and synaptic remodeling of AMPARs across all groups. Notably, resilient individuals exhibited robust involvement in cellular respiration pathways, indicating compensatory mechanisms and enhanced energy management. We further investigated the synaptic responses of CP-AMPARs in these groups by isolating and transplanting synaptic membranes from the parietal cortex into Xenopus laevis oocytes for analysis. Through activation and subsequent inhibition of AMPARs, we determined the contribution of CP-AMPARs to the overall response, revealing reduced CP-AMPARs responses in resilient individuals. Collectively, our findings provide insights into the structural and functional differences of CP-AMPARs in resilient individuals, potentially reflecting underlying structural or signaling changes identified in our proteomic analysis. Further investigations are warranted to fully understand the mechanisms underlying these alterations and their implications for the progression of AD.
Original languageEnglish (US)
StatePublished - 2023
EventSociety for Neuroscience: Neuroscience 2023 - Walter E. Washington Convention Center , Washington DC, United States
Duration: Nov 11 2023Nov 15 2023


ConferenceSociety for Neuroscience
Country/TerritoryUnited States
CityWashington DC
Internet address


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