Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology

Fernando Maestú, Willem de Haan, Marc Aurel Busche, Javier DeFelipe

Research output: Contribution to journalReview articleAcademicpeer-review

55 Citations (Scopus)


Our incomplete understanding of the link between Alzheimer's Disease pathology and symptomatology is a crucial obstacle for therapeutic success. Recently, translational studies have begun to connect the dots between protein alterations and deposition, brain network dysfunction and cognitive deficits. Disturbance of neuronal activity, and in particular an imbalance in underlying excitation/inhibition (E/I), appears early in AD, and can be regarded as forming a central link between structural brain pathology and cognitive dysfunction. While there are emerging (non-)pharmacological options to influence this imbalance, the complexity of human brain dynamics has hindered identification of an optimal approach. We suggest that focusing on the integration of neurophysiological aspects of AD at the micro-, meso- and macroscale, with the support of computational network modeling, can unite fundamental and clinical knowledge, provide a general framework, and suggest rational therapeutic targets.
Original languageEnglish
Article number101372
JournalAgeing Research Reviews
Publication statusPublished - 1 Aug 2021


  • Alzheimer's disease
  • Amyloid protein
  • Animal models
  • Computational neuroscience
  • Excitation/inhibition imbalance
  • Functional networks
  • Hyperexcitability
  • Hypersynchronization
  • Macro scale
  • Meso scale
  • Microscale
  • Tau protein

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