Deanna Protocol Ameliorates the Deficits in Human
iPSC
‐Cortical Neurons Carrying Familial Alzheimer's Mutation
Leticia Keler Soares, Gaurav Srivastava, Camden Dwelle, Brianna Waggoner, Vince Tedone, James J. Hickman, Xiufang Guo ABSTRACT
Aims
Deanna Protocol (DP) is an anaplerotic, mechanism‐based therapy designed to address impaired cellular energy flux. The present study aims to investigate the effects of DP in treating Alzheimer's disease (AD) by using cortical neurons derived from AD patient iPSCs carrying a PSEN1 mutation, while cortical neurons differentiated from iPSCs of a healthy subject serve as control.
Methods
PSEN1 cortical neurons were treated with DP acutely (24 h) and chronically (1–3 weeks). The effect of DP was assessed by utilizing TMRE assay for mitochondrial function, immunofluorescent staining for AD neuron morphological pathology, whole cell patch clamp for neuron electrophysiological property, and microelectrode array (MEA) analysis of long‐term potentiation (LTP) for neurocircuit function.
Results
PSEN1 cortical neurons demonstrated impaired mitochondrial function, elevated pathological biomarkers, reduced neurite complexity, altered electrophysiology, and decreased LTP. DP treatment significantly ameliorated all these phenotypes.
Conclusion
This study, while confirming iPSC‐ PSEN1 cortical neurons as a valid AD model, demonstrated the efficacy of DP on ameliorating structural and functional pathologies in AD neurons. It highlights that targeting energy production could be an effective approach in treating neurodegeneration in AD and suggests its potential efficacy in other neurodegenerative diseases.