Dendritic spines are lost in clusters in Alzheimer’s disease

Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are...

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Autores principales:	Mite Mijalkov, Giovanni Volpe, Isabel Fernaud-Espinosa, Javier DeFelipe, Joana B. Pereira, Paula Merino-Serrais
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d034dbf4fa34ac4b7eba3dd4ccfc10a
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spelling	oai:doaj.org-article:1d034dbf4fa34ac4b7eba3dd4ccfc10a2021-12-02T17:52:23ZDendritic spines are lost in clusters in Alzheimer’s disease10.1038/s41598-021-91726-x2045-2322https://doaj.org/article/1d034dbf4fa34ac4b7eba3dd4ccfc10a2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91726-xhttps://doaj.org/toc/2045-2322Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization.Mite MijalkovGiovanni VolpeIsabel Fernaud-EspinosaJavier DeFelipeJoana B. PereiraPaula Merino-SerraisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mite Mijalkov Giovanni Volpe Isabel Fernaud-Espinosa Javier DeFelipe Joana B. Pereira Paula Merino-Serrais Dendritic spines are lost in clusters in Alzheimer’s disease
description	Abstract Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by a deterioration of neuronal connectivity. The pathological accumulation of tau in neurons is one of the hallmarks of AD and has been connected to the loss of dendritic spines of pyramidal cells, which are the major targets of cortical excitatory synapses and key elements in memory storage. However, the detailed mechanisms underlying the loss of dendritic spines in individuals with AD are still unclear. Here, we used graph-theory approaches to compare the distribution of dendritic spines from neurons with and without tau pathology of AD individuals. We found that the presence of tau pathology determines the loss of dendritic spines in clusters, ruling out alternative models where spine loss occurs at random locations. Since memory storage has been associated with synaptic clusters, the present results provide a new insight into the mechanisms by which tau drives synaptic damage in AD, paving the way to memory deficits through alterations of spine organization.
format	article
author	Mite Mijalkov Giovanni Volpe Isabel Fernaud-Espinosa Javier DeFelipe Joana B. Pereira Paula Merino-Serrais
author_facet	Mite Mijalkov Giovanni Volpe Isabel Fernaud-Espinosa Javier DeFelipe Joana B. Pereira Paula Merino-Serrais
author_sort	Mite Mijalkov
title	Dendritic spines are lost in clusters in Alzheimer’s disease
title_short	Dendritic spines are lost in clusters in Alzheimer’s disease
title_full	Dendritic spines are lost in clusters in Alzheimer’s disease
title_fullStr	Dendritic spines are lost in clusters in Alzheimer’s disease
title_full_unstemmed	Dendritic spines are lost in clusters in Alzheimer’s disease
title_sort	dendritic spines are lost in clusters in alzheimer’s disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/1d034dbf4fa34ac4b7eba3dd4ccfc10a
work_keys_str_mv	AT mitemijalkov dendriticspinesarelostinclustersinalzheimersdisease AT giovannivolpe dendriticspinesarelostinclustersinalzheimersdisease AT isabelfernaudespinosa dendriticspinesarelostinclustersinalzheimersdisease AT javierdefelipe dendriticspinesarelostinclustersinalzheimersdisease AT joanabpereira dendriticspinesarelostinclustersinalzheimersdisease AT paulamerinoserrais dendriticspinesarelostinclustersinalzheimersdisease
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Dendritic spines are lost in clusters in Alzheimer’s disease

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