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Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease
Corpora amylacea (CA) and their murine analogs, periodic acid Schiff (PAS) granules, are age-related, carbohydrate-rich structures that serve as waste repositories for aggregated proteins, damaged cellular organelles, and other cellular debris. The structure, morphology, and suspected functions of C...
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/PMC9361643/ https://www.ncbi.nlm.nih.gov/pubmed/35941704 http://dx.doi.org/10.1186/s40478-022-01409-5 |
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author | Wander, Connor M. Tsujimoto, Tamy Harumy Moraes Ervin, John F. Wang, Chanung Maranto, Spencer M. Bhat, Vanya Dallmeier, Julian D. Wang, Shih-Hsiu Jerry Lin, Feng-Chang Scott, William K. Holtzman, David M. Cohen, Todd J. |
author_facet | Wander, Connor M. Tsujimoto, Tamy Harumy Moraes Ervin, John F. Wang, Chanung Maranto, Spencer M. Bhat, Vanya Dallmeier, Julian D. Wang, Shih-Hsiu Jerry Lin, Feng-Chang Scott, William K. Holtzman, David M. Cohen, Todd J. |
author_sort | Wander, Connor M. |
collection | PubMed |
description | Corpora amylacea (CA) and their murine analogs, periodic acid Schiff (PAS) granules, are age-related, carbohydrate-rich structures that serve as waste repositories for aggregated proteins, damaged cellular organelles, and other cellular debris. The structure, morphology, and suspected functions of CA in the brain imply disease relevance. Despite this, the link between CA and age-related neurodegenerative diseases, particularly Alzheimer’s disease (AD), remains poorly defined. We performed a neuropathological analysis of mouse PAS granules and human CA and correlated these findings with AD progression. Increased PAS granule density was observed in symptomatic tau transgenic mice and APOE knock-in mice. Using a cohort of postmortem AD brain samples, we examined CA in cognitively normal and dementia patients across Braak stages with varying APOE status. We identified a Braak-stage dependent bimodal distribution of CA in the dentate gyrus, with CA accumulating and peaking by Braak stages II–III, then steadily declining with increasing tau burden. Refined analysis revealed an association of CA levels with both cognition and APOE status. Finally, tau was detected in whole CA present in human patient cerebrospinal fluid, highlighting CA-tau as a plausible prodromal AD biomarker. Our study connects hallmarks of the aging brain with the emergence of AD pathology and suggests that CA may act as a compensatory factor that becomes depleted with advancing tau burden. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-022-01409-5. |
format | Online Article Text |
id | pubmed-9361643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-93616432022-08-10 Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease Wander, Connor M. Tsujimoto, Tamy Harumy Moraes Ervin, John F. Wang, Chanung Maranto, Spencer M. Bhat, Vanya Dallmeier, Julian D. Wang, Shih-Hsiu Jerry Lin, Feng-Chang Scott, William K. Holtzman, David M. Cohen, Todd J. Acta Neuropathol Commun Research Corpora amylacea (CA) and their murine analogs, periodic acid Schiff (PAS) granules, are age-related, carbohydrate-rich structures that serve as waste repositories for aggregated proteins, damaged cellular organelles, and other cellular debris. The structure, morphology, and suspected functions of CA in the brain imply disease relevance. Despite this, the link between CA and age-related neurodegenerative diseases, particularly Alzheimer’s disease (AD), remains poorly defined. We performed a neuropathological analysis of mouse PAS granules and human CA and correlated these findings with AD progression. Increased PAS granule density was observed in symptomatic tau transgenic mice and APOE knock-in mice. Using a cohort of postmortem AD brain samples, we examined CA in cognitively normal and dementia patients across Braak stages with varying APOE status. We identified a Braak-stage dependent bimodal distribution of CA in the dentate gyrus, with CA accumulating and peaking by Braak stages II–III, then steadily declining with increasing tau burden. Refined analysis revealed an association of CA levels with both cognition and APOE status. Finally, tau was detected in whole CA present in human patient cerebrospinal fluid, highlighting CA-tau as a plausible prodromal AD biomarker. Our study connects hallmarks of the aging brain with the emergence of AD pathology and suggests that CA may act as a compensatory factor that becomes depleted with advancing tau burden. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40478-022-01409-5. BioMed Central 2022-08-08 /pmc/articles/PMC9361643/ /pubmed/35941704 http://dx.doi.org/10.1186/s40478-022-01409-5 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 Wander, Connor M. Tsujimoto, Tamy Harumy Moraes Ervin, John F. Wang, Chanung Maranto, Spencer M. Bhat, Vanya Dallmeier, Julian D. Wang, Shih-Hsiu Jerry Lin, Feng-Chang Scott, William K. Holtzman, David M. Cohen, Todd J. Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease |
title | Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease |
title_full | Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease |
title_fullStr | Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease |
title_full_unstemmed | Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease |
title_short | Corpora amylacea are associated with tau burden and cognitive status in Alzheimer’s disease |
title_sort | corpora amylacea are associated with tau burden and cognitive status in alzheimer’s disease |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9361643/ https://www.ncbi.nlm.nih.gov/pubmed/35941704 http://dx.doi.org/10.1186/s40478-022-01409-5 |
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