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

Maestú, F; de Haan, W; Busche, MA; DeFelipe, J; (2021) Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology. Ageing Research Reviews , 69 , Article 101372. 10.1016/j.arr.2021.101372. Green open access

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Abstract

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.

Type: Article
Title: Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.arr.2021.101372
Publisher version: http://dx.doi.org/10.1016/j.arr.2021.101372
Language: English
Additional information: © 2021 Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: Alzheimer’s disease, Amyloid protein, Animal models, Computational neuroscience, Excitation/inhibition imbalance, Functional networks, Hyperexcitability, Hypersynchronization, Macro scale, Meso scale, Microscale, Tau protein
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10129223
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