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Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease
Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aβ) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and la...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056016/ https://www.ncbi.nlm.nih.gov/pubmed/33889121 http://dx.doi.org/10.3389/fneur.2021.543866 |
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author | Ikeda, Masaki Kodaira, Sayaka Kasahara, Hiroo Takai, Eriko Nagashima, Kazuaki Fujita, Yukio Makioka, Kouki Hirayanagi, Kimitoshi Furuta, Natsumi Furuta, Minori Sanada, Etsuko Kobayashi, Ayumi Harigaya, Yasuo Nagamine, Shun Hattori, Noriaki Tashiro, Yuichi Kishi, Kazuhiro Shimada, Hirotaka Suto, Takayuki Tanaka, Hisashi Sakai, Yasujiro Yamazaki, Tsuneo Tanaka, Yukiko Aihara, Yuko Amari, Masakuni Yamaguchi, Haruyasu Okamoto, Koichi Takatama, Masamitsu Ishii, Kenji Higuchi, Tetsuya Tsushima, Yoshito Ikeda, Yoshio |
author_facet | Ikeda, Masaki Kodaira, Sayaka Kasahara, Hiroo Takai, Eriko Nagashima, Kazuaki Fujita, Yukio Makioka, Kouki Hirayanagi, Kimitoshi Furuta, Natsumi Furuta, Minori Sanada, Etsuko Kobayashi, Ayumi Harigaya, Yasuo Nagamine, Shun Hattori, Noriaki Tashiro, Yuichi Kishi, Kazuhiro Shimada, Hirotaka Suto, Takayuki Tanaka, Hisashi Sakai, Yasujiro Yamazaki, Tsuneo Tanaka, Yukiko Aihara, Yuko Amari, Masakuni Yamaguchi, Haruyasu Okamoto, Koichi Takatama, Masamitsu Ishii, Kenji Higuchi, Tetsuya Tsushima, Yoshito Ikeda, Yoshio |
author_sort | Ikeda, Masaki |
collection | PubMed |
description | Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aβ) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aβ1-42, Aβ1-40, Aβ1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by (99m)Tc-ethyl cysteinate dimer single photon emission computerized tomography ((99m)Tc ECD-SPECT), as well as the mean cortical standard uptake value ratio by (11)C-labeled Pittsburgh Compound B-positron emission tomography ((11)C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aβ1-38, Aβ1-40, Aβ1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant. |
format | Online Article Text |
id | pubmed-8056016 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-80560162021-04-21 Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease Ikeda, Masaki Kodaira, Sayaka Kasahara, Hiroo Takai, Eriko Nagashima, Kazuaki Fujita, Yukio Makioka, Kouki Hirayanagi, Kimitoshi Furuta, Natsumi Furuta, Minori Sanada, Etsuko Kobayashi, Ayumi Harigaya, Yasuo Nagamine, Shun Hattori, Noriaki Tashiro, Yuichi Kishi, Kazuhiro Shimada, Hirotaka Suto, Takayuki Tanaka, Hisashi Sakai, Yasujiro Yamazaki, Tsuneo Tanaka, Yukiko Aihara, Yuko Amari, Masakuni Yamaguchi, Haruyasu Okamoto, Koichi Takatama, Masamitsu Ishii, Kenji Higuchi, Tetsuya Tsushima, Yoshito Ikeda, Yoshio Front Neurol Neurology Lobar cerebral microbleeds (CMBs) in Alzheimer's disease (AD) are associated with cerebral amyloid angiopathy (CAA) due to vascular amyloid beta (Aβ) deposits. However, the relationship between lobar CMBs and clinical subtypes of AD remains unknown. Here, we enrolled patients with early- and late-onset amnestic dominant AD, logopenic variant of primary progressive aphasia (lvPPA) and posterior cortical atrophy (PCA) who were compatible with the AD criteria. We then examined the levels of cerebrospinal fluid (CSF) biomarkers [Aβ1-42, Aβ1-40, Aβ1-38, phosphorylated tau 181 (P-Tau), total tau (T-Tau), neurofilament light chain (NFL), and chitinase 3-like 1 protein (YKL-40)], analyzed the number and localization of CMBs, and measured the cerebral blood flow (CBF) volume by (99m)Tc-ethyl cysteinate dimer single photon emission computerized tomography ((99m)Tc ECD-SPECT), as well as the mean cortical standard uptake value ratio by (11)C-labeled Pittsburgh Compound B-positron emission tomography ((11)C PiB-PET). Lobar CMBs in lvPPA were distributed in the temporal, frontal, and parietal lobes with the left side predominance, while the CBF volume in lvPPA significantly decreased in the left temporal area, where the number of lobar CMBs and the CBF volumes showed a significant inversely correlation. The CSF levels of NFL in lvPPA were significantly higher compared to the other AD subtypes and non-demented subjects. The numbers of lobar CMBs significantly increased the CSF levels of NFL in the total AD patients, additionally, among AD subtypes, the CSF levels of NFL in lvPPA predominantly were higher by increasing number of lobar CMBs. On the other hand, the CSF levels of Aβ1-38, Aβ1-40, Aβ1-42, P-Tau, and T-Tau were lower by increasing number of lobar CMBs in the total AD patients. These findings may suggest that aberrant brain hypoperfusion in lvPPA was derived from the brain atrophy due to neurodegeneration, and possibly may involve the aberrant microcirculation causing by lobar CMBs and cerebrovascular injuries, with the left side dominance, consequently leading to a clinical phenotype of logopenic variant. Frontiers Media S.A. 2021-04-06 /pmc/articles/PMC8056016/ /pubmed/33889121 http://dx.doi.org/10.3389/fneur.2021.543866 Text en Copyright © 2021 Ikeda, Kodaira, Kasahara, Takai, Nagashima, Fujita, Makioka, Hirayanagi, Furuta, Furuta, Sanada, Kobayashi, Harigaya, Nagamine, Hattori, Tashiro, Kishi, Shimada, Suto, Tanaka, Sakai, Yamazaki, Tanaka, Aihara, Amari, Yamaguchi, Okamoto, Takatama, Ishii, Higuchi, Tsushima and Ikeda. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology Ikeda, Masaki Kodaira, Sayaka Kasahara, Hiroo Takai, Eriko Nagashima, Kazuaki Fujita, Yukio Makioka, Kouki Hirayanagi, Kimitoshi Furuta, Natsumi Furuta, Minori Sanada, Etsuko Kobayashi, Ayumi Harigaya, Yasuo Nagamine, Shun Hattori, Noriaki Tashiro, Yuichi Kishi, Kazuhiro Shimada, Hirotaka Suto, Takayuki Tanaka, Hisashi Sakai, Yasujiro Yamazaki, Tsuneo Tanaka, Yukiko Aihara, Yuko Amari, Masakuni Yamaguchi, Haruyasu Okamoto, Koichi Takatama, Masamitsu Ishii, Kenji Higuchi, Tetsuya Tsushima, Yoshito Ikeda, Yoshio Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease |
title | Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease |
title_full | Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease |
title_fullStr | Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease |
title_full_unstemmed | Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease |
title_short | Cerebral Microbleeds, Cerebrospinal Fluid, and Neuroimaging Markers in Clinical Subtypes of Alzheimer's Disease |
title_sort | cerebral microbleeds, cerebrospinal fluid, and neuroimaging markers in clinical subtypes of alzheimer's disease |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056016/ https://www.ncbi.nlm.nih.gov/pubmed/33889121 http://dx.doi.org/10.3389/fneur.2021.543866 |
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