Cargando…

Three-dimensional analysis of synaptic organization in the hippocampal CA1 field in Alzheimer’s disease

Alzheimer’s disease is the most common form of dementia, characterized by a persistent and progressive impairment of cognitive functions. Alzheimer’s disease is typically associated with extracellular deposits of amyloid-β peptide and accumulation of abnormally phosphorylated tau protein inside neur...

Descripción completa

Detalles Bibliográficos
Autores principales: Montero-Crespo, Marta, Domínguez-Álvaro, Marta, Alonso-Nanclares, Lidia, DeFelipe, Javier, Blazquez-Llorca, Lidia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240746/
https://www.ncbi.nlm.nih.gov/pubmed/33324984
http://dx.doi.org/10.1093/brain/awaa406
_version_ 1783715268303781888
author Montero-Crespo, Marta
Domínguez-Álvaro, Marta
Alonso-Nanclares, Lidia
DeFelipe, Javier
Blazquez-Llorca, Lidia
author_facet Montero-Crespo, Marta
Domínguez-Álvaro, Marta
Alonso-Nanclares, Lidia
DeFelipe, Javier
Blazquez-Llorca, Lidia
author_sort Montero-Crespo, Marta
collection PubMed
description Alzheimer’s disease is the most common form of dementia, characterized by a persistent and progressive impairment of cognitive functions. Alzheimer’s disease is typically associated with extracellular deposits of amyloid-β peptide and accumulation of abnormally phosphorylated tau protein inside neurons (amyloid-β and neurofibrillary pathologies). It has been proposed that these pathologies cause neuronal degeneration and synaptic alterations, which are thought to constitute the major neurobiological basis of cognitive dysfunction in Alzheimer’s disease. The hippocampal formation is especially vulnerable in the early stages of Alzheimer’s disease. However, the vast majority of electron microscopy studies have been performed in animal models. In the present study, we performed an extensive 3D study of the neuropil to investigate the synaptic organization in the stratum pyramidale and radiatum in the CA1 field of Alzheimer’s disease cases with different stages of the disease, using focused ion beam/scanning electron microscopy (FIB/SEM). In cases with early stages of Alzheimer’s disease, the synapse morphology looks normal and we observed no significant differences between control and Alzheimer’s disease cases regarding the synaptic density, the ratio of excitatory and inhibitory synapses, or the spatial distribution of synapses. However, differences in the distribution of postsynaptic targets and synaptic shapes were found. Furthermore, a lower proportion of larger excitatory synapses in both strata were found in Alzheimer’s disease cases. Individuals in late stages of the disease suffered the most severe synaptic alterations, including a decrease in synaptic density and morphological alterations of the remaining synapses. Since Alzheimer’s disease cases show cortical atrophy, our data indicate a reduction in the total number (but not the density) of synapses at early stages of the disease, with this reduction being much more accentuated in subjects with late stages of Alzheimer’s disease. The observed synaptic alterations may represent a structural basis for the progressive learning and memory dysfunctions seen in Alzheimer’s disease cases.
format Online
Article
Text
id pubmed-8240746
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-82407462021-06-30 Three-dimensional analysis of synaptic organization in the hippocampal CA1 field in Alzheimer’s disease Montero-Crespo, Marta Domínguez-Álvaro, Marta Alonso-Nanclares, Lidia DeFelipe, Javier Blazquez-Llorca, Lidia Brain Original Articles Alzheimer’s disease is the most common form of dementia, characterized by a persistent and progressive impairment of cognitive functions. Alzheimer’s disease is typically associated with extracellular deposits of amyloid-β peptide and accumulation of abnormally phosphorylated tau protein inside neurons (amyloid-β and neurofibrillary pathologies). It has been proposed that these pathologies cause neuronal degeneration and synaptic alterations, which are thought to constitute the major neurobiological basis of cognitive dysfunction in Alzheimer’s disease. The hippocampal formation is especially vulnerable in the early stages of Alzheimer’s disease. However, the vast majority of electron microscopy studies have been performed in animal models. In the present study, we performed an extensive 3D study of the neuropil to investigate the synaptic organization in the stratum pyramidale and radiatum in the CA1 field of Alzheimer’s disease cases with different stages of the disease, using focused ion beam/scanning electron microscopy (FIB/SEM). In cases with early stages of Alzheimer’s disease, the synapse morphology looks normal and we observed no significant differences between control and Alzheimer’s disease cases regarding the synaptic density, the ratio of excitatory and inhibitory synapses, or the spatial distribution of synapses. However, differences in the distribution of postsynaptic targets and synaptic shapes were found. Furthermore, a lower proportion of larger excitatory synapses in both strata were found in Alzheimer’s disease cases. Individuals in late stages of the disease suffered the most severe synaptic alterations, including a decrease in synaptic density and morphological alterations of the remaining synapses. Since Alzheimer’s disease cases show cortical atrophy, our data indicate a reduction in the total number (but not the density) of synapses at early stages of the disease, with this reduction being much more accentuated in subjects with late stages of Alzheimer’s disease. The observed synaptic alterations may represent a structural basis for the progressive learning and memory dysfunctions seen in Alzheimer’s disease cases. Oxford University Press 2021-01-19 /pmc/articles/PMC8240746/ /pubmed/33324984 http://dx.doi.org/10.1093/brain/awaa406 Text en © The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Montero-Crespo, Marta
Domínguez-Álvaro, Marta
Alonso-Nanclares, Lidia
DeFelipe, Javier
Blazquez-Llorca, Lidia
Three-dimensional analysis of synaptic organization in the hippocampal CA1 field in Alzheimer’s disease
title Three-dimensional analysis of synaptic organization in the hippocampal CA1 field in Alzheimer’s disease
title_full Three-dimensional analysis of synaptic organization in the hippocampal CA1 field in Alzheimer’s disease
title_fullStr Three-dimensional analysis of synaptic organization in the hippocampal CA1 field in Alzheimer’s disease
title_full_unstemmed Three-dimensional analysis of synaptic organization in the hippocampal CA1 field in Alzheimer’s disease
title_short Three-dimensional analysis of synaptic organization in the hippocampal CA1 field in Alzheimer’s disease
title_sort three-dimensional analysis of synaptic organization in the hippocampal ca1 field in alzheimer’s disease
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240746/
https://www.ncbi.nlm.nih.gov/pubmed/33324984
http://dx.doi.org/10.1093/brain/awaa406
work_keys_str_mv AT monterocrespomarta threedimensionalanalysisofsynapticorganizationinthehippocampalca1fieldinalzheimersdisease
AT dominguezalvaromarta threedimensionalanalysisofsynapticorganizationinthehippocampalca1fieldinalzheimersdisease
AT alonsonanclareslidia threedimensionalanalysisofsynapticorganizationinthehippocampalca1fieldinalzheimersdisease
AT defelipejavier threedimensionalanalysisofsynapticorganizationinthehippocampalca1fieldinalzheimersdisease
AT blazquezllorcalidia threedimensionalanalysisofsynapticorganizationinthehippocampalca1fieldinalzheimersdisease