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Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease
Alzheimer’s disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal ento...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854528/ https://www.ncbi.nlm.nih.gov/pubmed/33432193 http://dx.doi.org/10.1038/s41593-020-00764-7 |
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author | Leng, Kun Li, Emmy Eser, Rana Piergies, Antonia Sit, Rene Tan, Michelle Neff, Norma Li, Song Hua Rodriguez, Roberta Diehl Suemoto, Claudia Kimie Leite, Renata Elaine Paraizo Ehrenberg, Alexander J. Pasqualucci, Carlos A. Seeley, William W. Spina, Salvatore Heinsen, Helmut Grinberg, Lea T. Kampmann, Martin |
author_facet | Leng, Kun Li, Emmy Eser, Rana Piergies, Antonia Sit, Rene Tan, Michelle Neff, Norma Li, Song Hua Rodriguez, Roberta Diehl Suemoto, Claudia Kimie Leite, Renata Elaine Paraizo Ehrenberg, Alexander J. Pasqualucci, Carlos A. Seeley, William W. Spina, Salvatore Heinsen, Helmut Grinberg, Lea T. Kampmann, Martin |
author_sort | Leng, Kun |
collection | PubMed |
description | Alzheimer’s disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus – brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively – from postmortem brains spanning the progression of AD-type tau neurofibrillary pathology. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex, and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience. |
format | Online Article Text |
id | pubmed-7854528 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
record_format | MEDLINE/PubMed |
spelling | pubmed-78545282021-07-11 Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease Leng, Kun Li, Emmy Eser, Rana Piergies, Antonia Sit, Rene Tan, Michelle Neff, Norma Li, Song Hua Rodriguez, Roberta Diehl Suemoto, Claudia Kimie Leite, Renata Elaine Paraizo Ehrenberg, Alexander J. Pasqualucci, Carlos A. Seeley, William W. Spina, Salvatore Heinsen, Helmut Grinberg, Lea T. Kampmann, Martin Nat Neurosci Article Alzheimer’s disease (AD) is characterized by the selective vulnerability of specific neuronal populations, the molecular signatures of which are largely unknown. To identify and characterize selectively vulnerable neuronal populations, we used single-nucleus RNA sequencing to profile the caudal entorhinal cortex and the superior frontal gyrus – brain regions where neurofibrillary inclusions and neuronal loss occur early and late in AD, respectively – from postmortem brains spanning the progression of AD-type tau neurofibrillary pathology. We identified RORB as a marker of selectively vulnerable excitatory neurons in the entorhinal cortex, and subsequently validated their depletion and selective susceptibility to neurofibrillary inclusions during disease progression using quantitative neuropathological methods. We also discovered an astrocyte subpopulation, likely representing reactive astrocytes, characterized by decreased expression of genes involved in homeostatic functions. Our characterization of selectively vulnerable neurons in AD paves the way for future mechanistic studies of selective vulnerability and potential therapeutic strategies for enhancing neuronal resilience. 2021-01-11 2021-02 /pmc/articles/PMC7854528/ /pubmed/33432193 http://dx.doi.org/10.1038/s41593-020-00764-7 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Leng, Kun Li, Emmy Eser, Rana Piergies, Antonia Sit, Rene Tan, Michelle Neff, Norma Li, Song Hua Rodriguez, Roberta Diehl Suemoto, Claudia Kimie Leite, Renata Elaine Paraizo Ehrenberg, Alexander J. Pasqualucci, Carlos A. Seeley, William W. Spina, Salvatore Heinsen, Helmut Grinberg, Lea T. Kampmann, Martin Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease |
title | Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease |
title_full | Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease |
title_fullStr | Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease |
title_full_unstemmed | Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease |
title_short | Molecular characterization of selectively vulnerable neurons in Alzheimer’s Disease |
title_sort | molecular characterization of selectively vulnerable neurons in alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7854528/ https://www.ncbi.nlm.nih.gov/pubmed/33432193 http://dx.doi.org/10.1038/s41593-020-00764-7 |
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