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Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer’s disease
INTRODUCTION: Cerebrovascular pathologies including cerebral amyloid angiopathy (CAA) and blood-brain barrier (BBB) dysregulation are prominent features in the majority of Alzheimer’s disease (AD) cases. METHODS: We performed neuropathologic and biochemical studies on a large, neuropathologically co...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103951/ https://www.ncbi.nlm.nih.gov/pubmed/32827351 http://dx.doi.org/10.1002/alz.12104 |
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author | Liu, Chia-Chen Yamazaki, Yu Heckman, Michael G. Martens, Yuka A. Jia, Lin Yamazaki, Akari Diehl, Nancy N. Zhao, Jing Zhao, Na DeTure, Michael Davis, Mary D. Felton, Lindsey M. Qiao, Wenhui Li, Yonghe Li, Hongmei Fu, Yuan Wang, Na Wren, Melissa Aikawa, Tomonori Holm, Marie-Louise Oue, Hiroshi Linares, Cynthia Allen, Mariet Carrasquillo, Minerva M. Murray, Melissa E. Petersen, Ronald C. Ertekin-Taner, Nilüfer Dickson, Dennis W. Kanekiyo, Takahisa Bu, Guojun |
author_facet | Liu, Chia-Chen Yamazaki, Yu Heckman, Michael G. Martens, Yuka A. Jia, Lin Yamazaki, Akari Diehl, Nancy N. Zhao, Jing Zhao, Na DeTure, Michael Davis, Mary D. Felton, Lindsey M. Qiao, Wenhui Li, Yonghe Li, Hongmei Fu, Yuan Wang, Na Wren, Melissa Aikawa, Tomonori Holm, Marie-Louise Oue, Hiroshi Linares, Cynthia Allen, Mariet Carrasquillo, Minerva M. Murray, Melissa E. Petersen, Ronald C. Ertekin-Taner, Nilüfer Dickson, Dennis W. Kanekiyo, Takahisa Bu, Guojun |
author_sort | Liu, Chia-Chen |
collection | PubMed |
description | INTRODUCTION: Cerebrovascular pathologies including cerebral amyloid angiopathy (CAA) and blood-brain barrier (BBB) dysregulation are prominent features in the majority of Alzheimer’s disease (AD) cases. METHODS: We performed neuropathologic and biochemical studies on a large, neuropathologically confirmed human AD cohort (N = 469). Amounts of endothelial tight junction proteins claudin-5 (CLDN5) and occludin (OCLN), and major AD-related molecules (amyloid beta [Aβ40], Aβ42, tau, p-tau, and apolipoprotein E) in the temporal cortex were assessed by ELISA. RESULTS: Higher levels of soluble tau, insoluble p-tau, and apolipoprotein E (apoE) were independently correlated with lower levels of endothelial tight junction proteins CLDN5 and OCLN in AD brains. Although high Aβ40 levels, APOE ε4, and male sex were predominantly associated with exacerbated CAA severity, those factors did not influence tight junction protein levels. DISCUSSION: Refining the molecular mechanisms connecting tau, Aβ, and apoE with cerebrovascular pathologies is critical for greater understanding of AD pathogenesis and establishing effective therapeutic interventions for the disease. |
format | Online Article Text |
id | pubmed-8103951 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-81039512021-05-07 Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer’s disease Liu, Chia-Chen Yamazaki, Yu Heckman, Michael G. Martens, Yuka A. Jia, Lin Yamazaki, Akari Diehl, Nancy N. Zhao, Jing Zhao, Na DeTure, Michael Davis, Mary D. Felton, Lindsey M. Qiao, Wenhui Li, Yonghe Li, Hongmei Fu, Yuan Wang, Na Wren, Melissa Aikawa, Tomonori Holm, Marie-Louise Oue, Hiroshi Linares, Cynthia Allen, Mariet Carrasquillo, Minerva M. Murray, Melissa E. Petersen, Ronald C. Ertekin-Taner, Nilüfer Dickson, Dennis W. Kanekiyo, Takahisa Bu, Guojun Alzheimers Dement Article INTRODUCTION: Cerebrovascular pathologies including cerebral amyloid angiopathy (CAA) and blood-brain barrier (BBB) dysregulation are prominent features in the majority of Alzheimer’s disease (AD) cases. METHODS: We performed neuropathologic and biochemical studies on a large, neuropathologically confirmed human AD cohort (N = 469). Amounts of endothelial tight junction proteins claudin-5 (CLDN5) and occludin (OCLN), and major AD-related molecules (amyloid beta [Aβ40], Aβ42, tau, p-tau, and apolipoprotein E) in the temporal cortex were assessed by ELISA. RESULTS: Higher levels of soluble tau, insoluble p-tau, and apolipoprotein E (apoE) were independently correlated with lower levels of endothelial tight junction proteins CLDN5 and OCLN in AD brains. Although high Aβ40 levels, APOE ε4, and male sex were predominantly associated with exacerbated CAA severity, those factors did not influence tight junction protein levels. DISCUSSION: Refining the molecular mechanisms connecting tau, Aβ, and apoE with cerebrovascular pathologies is critical for greater understanding of AD pathogenesis and establishing effective therapeutic interventions for the disease. 2020-08-22 2020-10 /pmc/articles/PMC8103951/ /pubmed/32827351 http://dx.doi.org/10.1002/alz.12104 Text en https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the Creative Commons Attribution (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Article Liu, Chia-Chen Yamazaki, Yu Heckman, Michael G. Martens, Yuka A. Jia, Lin Yamazaki, Akari Diehl, Nancy N. Zhao, Jing Zhao, Na DeTure, Michael Davis, Mary D. Felton, Lindsey M. Qiao, Wenhui Li, Yonghe Li, Hongmei Fu, Yuan Wang, Na Wren, Melissa Aikawa, Tomonori Holm, Marie-Louise Oue, Hiroshi Linares, Cynthia Allen, Mariet Carrasquillo, Minerva M. Murray, Melissa E. Petersen, Ronald C. Ertekin-Taner, Nilüfer Dickson, Dennis W. Kanekiyo, Takahisa Bu, Guojun Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer’s disease |
title | Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer’s disease |
title_full | Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer’s disease |
title_fullStr | Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer’s disease |
title_full_unstemmed | Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer’s disease |
title_short | Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer’s disease |
title_sort | tau and apolipoprotein e modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in alzheimer’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8103951/ https://www.ncbi.nlm.nih.gov/pubmed/32827351 http://dx.doi.org/10.1002/alz.12104 |
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