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Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology
- Source :
- Maestú, F, de Haan, W, Busche, M A & DeFelipe, J 2021, ' Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology ', Ageing Research Reviews, vol. 69, 101372 . https://doi.org/10.1016/j.arr.2021.101372, E-Prints Complutense. Archivo Institucional de la UCM, instname
- Publication Year :
- 2020
-
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.<br />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 (UKDRI1010). M.A.B. is also funded by a UK RI Future Leaders Fellowship (MR/S017003/1) and a grant from the right Focus 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 Investigacion ´ en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0066, Spain); theSpanish “Ministerio de Ciencia e Innovacion´ ”(grant PGC2018-094307-B-I00 and the Cajal Blue Brain Project [the Spanish partner of the Blue Brain Project initiative from EPFL, Switzerland]).
- Subjects :
- 0301 basic medicine
Aging
Microscale
Neurociencias
Tau protein
Hyperexcitability
tau Proteins
Disease
Biochemistry
Excitation/inhibition imbalance
03 medical and health sciences
0302 clinical medicine
Hypersynchronization
Alzheimer Disease
medicine
Premovement neuronal activity
Humans
Cognitive Dysfunction
Molecular Biology
Computational neuroscience
biology
Perspective (graphical)
Brain
Cognition
Human brain
Neurophysiology
Meso scale
Animal models
Macro scale
030104 developmental biology
medicine.anatomical_structure
Neurology
Functional networks
Amyloid protein
biology.protein
Psychology
Cognition Disorders
Alzheimer’s disease
Neuroscience
030217 neurology & neurosurgery
Biotechnology
Subjects
Details
- ISSN :
- 18729649
- Volume :
- 69
- Database :
- OpenAIRE
- Journal :
- Ageing research reviews
- Accession number :
- edsair.doi.dedup.....c4ec9bad517c30d05ee759d1463ec7a9