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Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease

Selective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patt...

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Autores principales: Crist, Angela M., Hinkle, Kelly M., Wang, Xue, Moloney, Christina M., Matchett, Billie J., Labuzan, Sydney A., Frankenhauser, Isabelle, Azu, Nkem O., Liesinger, Amanda M., Lesser, Elizabeth R., Serie, Daniel J., Quicksall, Zachary S., Patel, Tulsi A., Carnwath, Troy P., DeTure, Michael, Tang, Xiaojia, Petersen, Ronald C., Duara, Ranjan, Graff-Radford, Neill R., Allen, Mariet, Carrasquillo, Minerva M., Li, Hu, Ross, Owen A., Ertekin-Taner, Nilüfer, Dickson, Dennis W., Asmann, Yan W., Carter, Rickey E., Murray, Melissa E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055900/
https://www.ncbi.nlm.nih.gov/pubmed/33875655
http://dx.doi.org/10.1038/s41467-021-22399-3
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author Crist, Angela M.
Hinkle, Kelly M.
Wang, Xue
Moloney, Christina M.
Matchett, Billie J.
Labuzan, Sydney A.
Frankenhauser, Isabelle
Azu, Nkem O.
Liesinger, Amanda M.
Lesser, Elizabeth R.
Serie, Daniel J.
Quicksall, Zachary S.
Patel, Tulsi A.
Carnwath, Troy P.
DeTure, Michael
Tang, Xiaojia
Petersen, Ronald C.
Duara, Ranjan
Graff-Radford, Neill R.
Allen, Mariet
Carrasquillo, Minerva M.
Li, Hu
Ross, Owen A.
Ertekin-Taner, Nilüfer
Dickson, Dennis W.
Asmann, Yan W.
Carter, Rickey E.
Murray, Melissa E.
author_facet Crist, Angela M.
Hinkle, Kelly M.
Wang, Xue
Moloney, Christina M.
Matchett, Billie J.
Labuzan, Sydney A.
Frankenhauser, Isabelle
Azu, Nkem O.
Liesinger, Amanda M.
Lesser, Elizabeth R.
Serie, Daniel J.
Quicksall, Zachary S.
Patel, Tulsi A.
Carnwath, Troy P.
DeTure, Michael
Tang, Xiaojia
Petersen, Ronald C.
Duara, Ranjan
Graff-Radford, Neill R.
Allen, Mariet
Carrasquillo, Minerva M.
Li, Hu
Ross, Owen A.
Ertekin-Taner, Nilüfer
Dickson, Dennis W.
Asmann, Yan W.
Carter, Rickey E.
Murray, Melissa E.
author_sort Crist, Angela M.
collection PubMed
description Selective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.
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spelling pubmed-80559002021-05-11 Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease Crist, Angela M. Hinkle, Kelly M. Wang, Xue Moloney, Christina M. Matchett, Billie J. Labuzan, Sydney A. Frankenhauser, Isabelle Azu, Nkem O. Liesinger, Amanda M. Lesser, Elizabeth R. Serie, Daniel J. Quicksall, Zachary S. Patel, Tulsi A. Carnwath, Troy P. DeTure, Michael Tang, Xiaojia Petersen, Ronald C. Duara, Ranjan Graff-Radford, Neill R. Allen, Mariet Carrasquillo, Minerva M. Li, Hu Ross, Owen A. Ertekin-Taner, Nilüfer Dickson, Dennis W. Asmann, Yan W. Carter, Rickey E. Murray, Melissa E. Nat Commun Article Selective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression. Nature Publishing Group UK 2021-04-19 /pmc/articles/PMC8055900/ /pubmed/33875655 http://dx.doi.org/10.1038/s41467-021-22399-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Crist, Angela M.
Hinkle, Kelly M.
Wang, Xue
Moloney, Christina M.
Matchett, Billie J.
Labuzan, Sydney A.
Frankenhauser, Isabelle
Azu, Nkem O.
Liesinger, Amanda M.
Lesser, Elizabeth R.
Serie, Daniel J.
Quicksall, Zachary S.
Patel, Tulsi A.
Carnwath, Troy P.
DeTure, Michael
Tang, Xiaojia
Petersen, Ronald C.
Duara, Ranjan
Graff-Radford, Neill R.
Allen, Mariet
Carrasquillo, Minerva M.
Li, Hu
Ross, Owen A.
Ertekin-Taner, Nilüfer
Dickson, Dennis W.
Asmann, Yan W.
Carter, Rickey E.
Murray, Melissa E.
Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease
title Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease
title_full Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease
title_fullStr Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease
title_full_unstemmed Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease
title_short Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease
title_sort transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055900/
https://www.ncbi.nlm.nih.gov/pubmed/33875655
http://dx.doi.org/10.1038/s41467-021-22399-3
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