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Progression of Alzheimer's disease parallels unusual structural plasticity of human dentate granule cells
Alzheimer´s disease (AD), the most common form of dementia in industrialized countries, severely targets the hippocampal formation in humans and mouse models of this condition. The adult hippocampus hosts the continuous addition of new dentate granule cells (DGCs) in numerous mammalian species, incl...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426249/ https://www.ncbi.nlm.nih.gov/pubmed/36038918 http://dx.doi.org/10.1186/s40478-022-01431-7 |
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author | Márquez-Valadez, B. Rábano, A. Llorens-Martín, M. |
author_facet | Márquez-Valadez, B. Rábano, A. Llorens-Martín, M. |
author_sort | Márquez-Valadez, B. |
collection | PubMed |
description | Alzheimer´s disease (AD), the most common form of dementia in industrialized countries, severely targets the hippocampal formation in humans and mouse models of this condition. The adult hippocampus hosts the continuous addition of new dentate granule cells (DGCs) in numerous mammalian species, including humans. Although the morphology and positioning of DGCs within the granule cell layer (GCL) match their developmental origin in rodents, a similar correlation has not been reported in humans to date. Our data reveal that DGCs located in inner portions of the human GCL show shorter and less complex dendrites than those found in outer portions of this layer, which are presumably generated developmentally. Moreover, in AD patients, DGCs show early morphological alterations that are further aggravated as the disease progresses. An aberrantly increased number of DGCs with several primary apical dendrites is the first morphological change detected in patients at Braak-Tau I/II stages. This alteration persists throughout AD progression and leads to generalized dendritic atrophy at late stages of the disease. Our data reveal the distinct vulnerability of several morphological characteristics of DGCs located in the inner and outer portions of the GCL to AD and support the notion that the malfunction of the hippocampus is related to cognitive impairments in patients with AD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-022-01431-7. |
format | Online Article Text |
id | pubmed-9426249 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-94262492022-08-31 Progression of Alzheimer's disease parallels unusual structural plasticity of human dentate granule cells Márquez-Valadez, B. Rábano, A. Llorens-Martín, M. Acta Neuropathol Commun Research Alzheimer´s disease (AD), the most common form of dementia in industrialized countries, severely targets the hippocampal formation in humans and mouse models of this condition. The adult hippocampus hosts the continuous addition of new dentate granule cells (DGCs) in numerous mammalian species, including humans. Although the morphology and positioning of DGCs within the granule cell layer (GCL) match their developmental origin in rodents, a similar correlation has not been reported in humans to date. Our data reveal that DGCs located in inner portions of the human GCL show shorter and less complex dendrites than those found in outer portions of this layer, which are presumably generated developmentally. Moreover, in AD patients, DGCs show early morphological alterations that are further aggravated as the disease progresses. An aberrantly increased number of DGCs with several primary apical dendrites is the first morphological change detected in patients at Braak-Tau I/II stages. This alteration persists throughout AD progression and leads to generalized dendritic atrophy at late stages of the disease. Our data reveal the distinct vulnerability of several morphological characteristics of DGCs located in the inner and outer portions of the GCL to AD and support the notion that the malfunction of the hippocampus is related to cognitive impairments in patients with AD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-022-01431-7. BioMed Central 2022-08-29 /pmc/articles/PMC9426249/ /pubmed/36038918 http://dx.doi.org/10.1186/s40478-022-01431-7 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Márquez-Valadez, B. Rábano, A. Llorens-Martín, M. Progression of Alzheimer's disease parallels unusual structural plasticity of human dentate granule cells |
title | Progression of Alzheimer's disease parallels unusual structural plasticity of human dentate granule cells |
title_full | Progression of Alzheimer's disease parallels unusual structural plasticity of human dentate granule cells |
title_fullStr | Progression of Alzheimer's disease parallels unusual structural plasticity of human dentate granule cells |
title_full_unstemmed | Progression of Alzheimer's disease parallels unusual structural plasticity of human dentate granule cells |
title_short | Progression of Alzheimer's disease parallels unusual structural plasticity of human dentate granule cells |
title_sort | progression of alzheimer's disease parallels unusual structural plasticity of human dentate granule cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9426249/ https://www.ncbi.nlm.nih.gov/pubmed/36038918 http://dx.doi.org/10.1186/s40478-022-01431-7 |
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