Synapse loss and progress of Alzheimer’s disease -A network model

Abstract We present observational evidence from studies on primary cortical cultures from AD transgenic mice, APPSwe/PS1ΔE9 (APP/PS1) mice, for significant decrease in total spine density at DIV-15 and onward. This indicates reduction in potential healthy synapses and strength of connections among n...

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Autores principales:	G. Kashyap, D. Bapat, D. Das, R. Gowaikar, R. E. Amritkar, G. Rangarajan, V. Ravindranath, G. Ambika
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1536a4a95e344c3ba52a07cabdc745fe
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spelling	oai:doaj.org-article:1536a4a95e344c3ba52a07cabdc745fe2021-12-02T15:09:14ZSynapse loss and progress of Alzheimer’s disease -A network model10.1038/s41598-019-43076-y2045-2322https://doaj.org/article/1536a4a95e344c3ba52a07cabdc745fe2019-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-43076-yhttps://doaj.org/toc/2045-2322Abstract We present observational evidence from studies on primary cortical cultures from AD transgenic mice, APPSwe/PS1ΔE9 (APP/PS1) mice, for significant decrease in total spine density at DIV-15 and onward. This indicates reduction in potential healthy synapses and strength of connections among neurons. Based on this, a network model of neurons is developed, that explains the consequent loss of coordinated activity and transmission efficiency among neurons that manifests over time. The critical time when structural connectivity in the brain undergoes a phase-transition, from initial robustness to irreparable breakdown, is estimated from this model. We also show how the global efficiency of signal transmission in the network decreases over time. Moreover, the number of multiple paths of high efficiency decreases rapidly as the disease progresses, indicating loss of structural plasticity and inefficiency in choosing alternate paths or desired paths for any pattern of activity. Thus loss of spines caused by β-Amyloid (Aβ) peptide results in disintegration of the neuronal network over time with consequent cognitive dysfunctions in Alzheimer’s Disease (AD).G. KashyapD. BapatD. DasR. GowaikarR. E. AmritkarG. RangarajanV. RavindranathG. AmbikaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-9 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q G. Kashyap D. Bapat D. Das R. Gowaikar R. E. Amritkar G. Rangarajan V. Ravindranath G. Ambika Synapse loss and progress of Alzheimer’s disease -A network model
description	Abstract We present observational evidence from studies on primary cortical cultures from AD transgenic mice, APPSwe/PS1ΔE9 (APP/PS1) mice, for significant decrease in total spine density at DIV-15 and onward. This indicates reduction in potential healthy synapses and strength of connections among neurons. Based on this, a network model of neurons is developed, that explains the consequent loss of coordinated activity and transmission efficiency among neurons that manifests over time. The critical time when structural connectivity in the brain undergoes a phase-transition, from initial robustness to irreparable breakdown, is estimated from this model. We also show how the global efficiency of signal transmission in the network decreases over time. Moreover, the number of multiple paths of high efficiency decreases rapidly as the disease progresses, indicating loss of structural plasticity and inefficiency in choosing alternate paths or desired paths for any pattern of activity. Thus loss of spines caused by β-Amyloid (Aβ) peptide results in disintegration of the neuronal network over time with consequent cognitive dysfunctions in Alzheimer’s Disease (AD).
format	article
author	G. Kashyap D. Bapat D. Das R. Gowaikar R. E. Amritkar G. Rangarajan V. Ravindranath G. Ambika
author_facet	G. Kashyap D. Bapat D. Das R. Gowaikar R. E. Amritkar G. Rangarajan V. Ravindranath G. Ambika
author_sort	G. Kashyap
title	Synapse loss and progress of Alzheimer’s disease -A network model
title_short	Synapse loss and progress of Alzheimer’s disease -A network model
title_full	Synapse loss and progress of Alzheimer’s disease -A network model
title_fullStr	Synapse loss and progress of Alzheimer’s disease -A network model
title_full_unstemmed	Synapse loss and progress of Alzheimer’s disease -A network model
title_sort	synapse loss and progress of alzheimer’s disease -a network model
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/1536a4a95e344c3ba52a07cabdc745fe
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Synapse loss and progress of Alzheimer’s disease -A network model

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