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New insight into Alzheimer's disease: Light reverses Aβ-obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice

INTRODUCTION: Pharmacological therapies to treat Alzheimer's disease (AD) targeting “Aβ” have failed for over 100 years. Low levels of laser light can disassemble Aβ. In this study, we investigated the mechanisms that Aβ-blocked extracellular space (ECS) induces memory disorders in APP/PS1 tran...

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Autores principales: Yue, Xiangpei, Mei, Yufei, Zhang, Yun, Tong, Zheng, Cui, Dehua, Yang, Jun, Wang, Aibo, Wang, Rui, Fei, Xuechao, Ai, Li, Di, Yalan, Luo, Hongjun, Li, Hui, Luo, Wenhong, Lu, Yu, Li, Rui, Duan, Chunli, Gao, Ge, Yang, Hui, Sun, Binggui, He, Rongqiao, Song, Weihong, Han, Hongbin, Tong, Zhiqian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838540/
https://www.ncbi.nlm.nih.gov/pubmed/31720368
http://dx.doi.org/10.1016/j.trci.2019.09.007
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author Yue, Xiangpei
Mei, Yufei
Zhang, Yun
Tong, Zheng
Cui, Dehua
Yang, Jun
Wang, Aibo
Wang, Rui
Fei, Xuechao
Ai, Li
Di, Yalan
Luo, Hongjun
Li, Hui
Luo, Wenhong
Lu, Yu
Li, Rui
Duan, Chunli
Gao, Ge
Yang, Hui
Sun, Binggui
He, Rongqiao
Song, Weihong
Han, Hongbin
Tong, Zhiqian
author_facet Yue, Xiangpei
Mei, Yufei
Zhang, Yun
Tong, Zheng
Cui, Dehua
Yang, Jun
Wang, Aibo
Wang, Rui
Fei, Xuechao
Ai, Li
Di, Yalan
Luo, Hongjun
Li, Hui
Luo, Wenhong
Lu, Yu
Li, Rui
Duan, Chunli
Gao, Ge
Yang, Hui
Sun, Binggui
He, Rongqiao
Song, Weihong
Han, Hongbin
Tong, Zhiqian
author_sort Yue, Xiangpei
collection PubMed
description INTRODUCTION: Pharmacological therapies to treat Alzheimer's disease (AD) targeting “Aβ” have failed for over 100 years. Low levels of laser light can disassemble Aβ. In this study, we investigated the mechanisms that Aβ-blocked extracellular space (ECS) induces memory disorders in APP/PS1 transgenic mice and addressed whether red light (RL) at 630 nm rescues cognitive decline by reducing Aβ-disturbed flow of interstitial fluid (ISF). METHODS: We compared the heating effects on the brains of rats illuminated with laser light at 630, 680, and 810 nm for 40 minutes, respectively. Then, a light-emitting diode with red light at 630 nm (LED-RL) was selected to illuminate AD mice. The changes in the structure of ECS in the cortex were examined by fluorescent double labeling. The volumes of ECS and flow speed of ISF were quantified by magnetic resonance imaging. Spatial memory behaviors in mice were evaluated by the Morris water maze. Then, the brains were sampled for biochemical analysis. RESULTS: RL at 630 nm had the least heating effects than other wavelengths associated with ~49% penetration ratio into the brains. For the molecular mechanisms, Aβ could induce formaldehyde (FA) accumulation by inactivating FA dehydrogenase. Unexpectedly, in turn, FA accelerated Aβ deposition in the ECS. However, LED-RL treatment not only directly destroyed Aβ assembly in vitro and in vivo but also activated FA dehydrogenase to degrade FA and attenuated FA-facilitated Aβ aggregation. Subsequently, LED-RL markedly smashed Aβ deposition in the ECS, recovered the flow of ISF, and rescued cognitive functions in AD mice. DISCUSSION: Aβ-obstructed ISF flow is the direct reason for the failure of the developed medicine delivery from superficial into the deep brain in the treatment of AD. The phototherapy of LED-RL improves memory by reducing Aβ-blocked ECS and suggests that it is a promising noninvasive approach to treat AD.
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spelling pubmed-68385402019-11-12 New insight into Alzheimer's disease: Light reverses Aβ-obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice Yue, Xiangpei Mei, Yufei Zhang, Yun Tong, Zheng Cui, Dehua Yang, Jun Wang, Aibo Wang, Rui Fei, Xuechao Ai, Li Di, Yalan Luo, Hongjun Li, Hui Luo, Wenhong Lu, Yu Li, Rui Duan, Chunli Gao, Ge Yang, Hui Sun, Binggui He, Rongqiao Song, Weihong Han, Hongbin Tong, Zhiqian Alzheimers Dement (N Y) Featured Article INTRODUCTION: Pharmacological therapies to treat Alzheimer's disease (AD) targeting “Aβ” have failed for over 100 years. Low levels of laser light can disassemble Aβ. In this study, we investigated the mechanisms that Aβ-blocked extracellular space (ECS) induces memory disorders in APP/PS1 transgenic mice and addressed whether red light (RL) at 630 nm rescues cognitive decline by reducing Aβ-disturbed flow of interstitial fluid (ISF). METHODS: We compared the heating effects on the brains of rats illuminated with laser light at 630, 680, and 810 nm for 40 minutes, respectively. Then, a light-emitting diode with red light at 630 nm (LED-RL) was selected to illuminate AD mice. The changes in the structure of ECS in the cortex were examined by fluorescent double labeling. The volumes of ECS and flow speed of ISF were quantified by magnetic resonance imaging. Spatial memory behaviors in mice were evaluated by the Morris water maze. Then, the brains were sampled for biochemical analysis. RESULTS: RL at 630 nm had the least heating effects than other wavelengths associated with ~49% penetration ratio into the brains. For the molecular mechanisms, Aβ could induce formaldehyde (FA) accumulation by inactivating FA dehydrogenase. Unexpectedly, in turn, FA accelerated Aβ deposition in the ECS. However, LED-RL treatment not only directly destroyed Aβ assembly in vitro and in vivo but also activated FA dehydrogenase to degrade FA and attenuated FA-facilitated Aβ aggregation. Subsequently, LED-RL markedly smashed Aβ deposition in the ECS, recovered the flow of ISF, and rescued cognitive functions in AD mice. DISCUSSION: Aβ-obstructed ISF flow is the direct reason for the failure of the developed medicine delivery from superficial into the deep brain in the treatment of AD. The phototherapy of LED-RL improves memory by reducing Aβ-blocked ECS and suggests that it is a promising noninvasive approach to treat AD. Elsevier 2019-10-30 /pmc/articles/PMC6838540/ /pubmed/31720368 http://dx.doi.org/10.1016/j.trci.2019.09.007 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Featured Article
Yue, Xiangpei
Mei, Yufei
Zhang, Yun
Tong, Zheng
Cui, Dehua
Yang, Jun
Wang, Aibo
Wang, Rui
Fei, Xuechao
Ai, Li
Di, Yalan
Luo, Hongjun
Li, Hui
Luo, Wenhong
Lu, Yu
Li, Rui
Duan, Chunli
Gao, Ge
Yang, Hui
Sun, Binggui
He, Rongqiao
Song, Weihong
Han, Hongbin
Tong, Zhiqian
New insight into Alzheimer's disease: Light reverses Aβ-obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice
title New insight into Alzheimer's disease: Light reverses Aβ-obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice
title_full New insight into Alzheimer's disease: Light reverses Aβ-obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice
title_fullStr New insight into Alzheimer's disease: Light reverses Aβ-obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice
title_full_unstemmed New insight into Alzheimer's disease: Light reverses Aβ-obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice
title_short New insight into Alzheimer's disease: Light reverses Aβ-obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice
title_sort new insight into alzheimer's disease: light reverses aβ-obstructed interstitial fluid flow and ameliorates memory decline in app/ps1 mice
topic Featured Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6838540/
https://www.ncbi.nlm.nih.gov/pubmed/31720368
http://dx.doi.org/10.1016/j.trci.2019.09.007
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