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Article type: Research Article
Authors: García-Carlos, Carlos Antonioa | Basurto-Islas, Gustavod | Perry, Georgee | Mondragón-Rodríguez, Siddharthab; c; *
Affiliations: [a] UNAM Division of Neurosciences, Institute of Cellular Physiology, National Autonomous University of México, México City, México | [b] UAQ Centre for Applied Biomedical Research – CIBA, School of Medicine, Autonomous University of Querétaro, Querétaro, México | [c] CONAHCYT National Council for Science and Technology, México City, México | [d] UG University of Guanajuato, León, Guanajuato, México | [e] UTSA Neuroscience Institute and Department of Biology, College of Sciences, University of Texas at San Antonio, San Antonio, TX, USA
Correspondence: [*] Correspondence to: Siddhartha Mondragón Rodríguez, Centre for Applied Biomedical Research, UAQ, Carretera a Chichimequillas, Ejido Bolaños, 76140 Querétaro, Querétaro, México. Tel.: +442 192 1200; E-mail: [email protected].
Abstract: Background:Cognitive deficits observed in Alzheimer’s disease (AD) patients have been correlated with altered hippocampal activity. Although the mechanism remains under extensive study, neurofibrillary tangles and amyloid plaques have been proposed as responsible for brain activity alterations. Aiming to unveil the mechanism, researchers have developed several transgenic models of AD. Nevertheless, the variability in hippocampal oscillatory alterations found in different genetic backgrounds and ages remains unclear. Objective:To assess the oscillatory alterations in relation to animal developmental age and protein inclusion, amyloid-β (Aβ) load, and abnormally phosphorylated tau (pTau), we reviewed and analyzed the published data on peak power, frequency, and quantification of theta-gamma cross-frequency coupling (modulation index values). Methods:To ensure that the search was as current as possible, a systematic review was conducted to locate and abstract all studies published from January 2000 to February 2023 that involved in vivo hippocampal local field potential recording in transgenic mouse models of AD. Results:The presence of Aβ was associated with electrophysiological alterations that are mainly reflected in power increases, frequency decreases, and lower modulation index values. Concomitantly, pTau accumulation was associated with electrophysiological alterations that are mainly reflected in power decreases, frequency decreases, and no significant alterations in modulation index values. Conclusions:In this study, we showed that electrophysiological parameters are altered from prodromal stages to the late stages of pathology. Thus, we found that Aβ deposition is associated with brain network hyperexcitability, whereas pTau deposition mainly leads to brain network hypoexcitability in transgenic models
Keywords: Alzheimer’s disease, amyloid-β, cross-frequency coupling, hippocampus, network hyperexcitability, network hypoexcitability, oscillatory activity, phospho-tau
DOI: 10.3233/JAD-231365
Journal: Journal of Alzheimer's Disease, vol. 99, no. 2, pp. 595-607, 2024
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