@article{5d5591c90af3403f848ed17466a97d59,
title = "Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology",
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.",
keywords = "Alzheimer's disease, Amyloid protein, Animal models, Computational neuroscience, Excitation/inhibition imbalance, Functional networks, Hyperexcitability, Hypersynchronization, Macro scale, Meso scale, Microscale, Tau protein",
author = "Fernando Maest{\'u} and {de Haan}, Willem and Busche, {Marc Aurel} and Javier DeFelipe",
note = "Funding Information: M.A.B. is supported by the UK Dementia Research Institute which receives its funding from DRI Ltd , funded by the Medical Research Council, Alzheimer's Society and Alzheimer Research UK (UKDRI‐1010). M.A.B. is also funded by a UKRI Future Leaders Fellowship ( MR/S017003/1 ) and a grant from the BrightFocus Foundation ( A2019112S ). F.M is supported by the Spanish Minister of Science ( RTI2018-098762-B-C31 ), University of Texas Houston Research Staff grant, NIH−HCP (Connectomics of Aging Brain and Dementia). J.dF was supported by Centro de Investigaci{\'o}n en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0066, Spain); the Spanish “Ministerio de Ciencia e Innovaci{\'o}n” (grant PGC2018-094307-B-I00 and the Cajal Blue Brain Project [the Spanish partner of the Blue Brain Project initiative from EPFL, Switzerland]). Funding Information: M.A.B. is supported by the UK Dementia Research Institute which receives its funding from DRI Ltd, funded by the Medical Research Council, Alzheimer's Society and Alzheimer Research UK (UKDRI-1010). M.A.B. is also funded by a UKRI Future Leaders Fellowship (MR/S017003/1) and a grant from the BrightFocus Foundation (A2019112S). F.M is supported by the Spanish Minister of Science (RTI2018-098762-B-C31), University of Texas Houston Research Staff grant, NIH?HCP (Connectomics of Aging Brain and Dementia). J.dF was supported by Centro de Investigaci?n en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0066, Spain); theSpanish ?Ministerio de Ciencia e Innovaci?n?(grant PGC2018-094307-B-I00 and the Cajal Blue Brain Project [the Spanish partner of the Blue Brain Project initiative from EPFL, Switzerland]). Publisher Copyright: {\textcopyright} 2021 Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",
year = "2021",
month = aug,
day = "1",
doi = "https://doi.org/10.1016/j.arr.2021.101372",
language = "English",
volume = "69",
journal = "Ageing Research Reviews",
issn = "1568-1637",
publisher = "Elsevier Ireland Ltd",
}