Dendritic spines are lost in clusters in Alzheimer’s disease

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...

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Bibliographic Details
Published in:Scientific reports 2021-06, Vol.11 (1), p.12350-12350, Article 12350
Main Authors: Mijalkov, Mite, Volpe, Giovanni, Fernaud-Espinosa, Isabel, DeFelipe, Javier, Pereira, Joana B., Merino-Serrais, Paula
Format: Article
Language:English
Subjects:
631/378/116
631/378/2597
631/378/3920
Aged, 80 and over
Alzheimer Disease - pathology
Alzheimer's disease
Basic Medicine
Clinical Medicine
Dendritic spines
Dendritic Spines - metabolism
Dendritic Spines - pathology
Humanities and Social Sciences
Humans
Klinisk medicin
Male
Medical and Health Sciences
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
multidisciplinary
Neural networks
Neurodegenerative diseases
Neurologi
Neurology
Neurosciences
Neurovetenskaper
Pathology
Pyramidal cells
Science
Science (multidisciplinary)
Spine
Synapses
Tau protein
tau Proteins - metabolism
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-021-91726-x