New insight into Alzheimer's disease: Light reverses Aβ‐obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice
Abstract 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/...
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Wiley
2019-01-01
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| Series: | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
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| Online Access: | https://doi.org/10.1016/j.trci.2019.09.007 |
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| author | Xiangpei Yue Yufei Mei Yun Zhang Zheng Tong Dehua Cui Jun Yang Aibo Wang Rui Wang Xuechao Fei Li Ai Yalan Di Hongjun Luo Hui Li Wenhong Luo Yu Lu Rui Li Chunli Duan Ge Gao Hui Yang Binggui Sun Rongqiao He Weihong Song Hongbin Han Zhiqian Tong |
| author_facet | Xiangpei Yue Yufei Mei Yun Zhang Zheng Tong Dehua Cui Jun Yang Aibo Wang Rui Wang Xuechao Fei Li Ai Yalan Di Hongjun Luo Hui Li Wenhong Luo Yu Lu Rui Li Chunli Duan Ge Gao Hui Yang Binggui Sun Rongqiao He Weihong Song Hongbin Han Zhiqian Tong |
| author_sort | Xiangpei Yue |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-7917b9a62d0944cfb44edf4dae35b608 |
| institution | DOAJ |
| issn | 2352-8737 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Alzheimer’s & Dementia: Translational Research & Clinical Interventions |
| spelling | doaj-art-7917b9a62d0944cfb44edf4dae35b6082025-08-20T03:22:00ZengWileyAlzheimer’s & Dementia: Translational Research & Clinical Interventions2352-87372019-01-015167168410.1016/j.trci.2019.09.007New insight into Alzheimer's disease: Light reverses Aβ‐obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 miceXiangpei Yue0Yufei Mei1Yun Zhang2Zheng Tong3Dehua Cui4Jun Yang5Aibo Wang6Rui Wang7Xuechao Fei8Li Ai9Yalan Di10Hongjun Luo11Hui Li12Wenhong Luo13Yu Lu14Rui Li15Chunli Duan16Ge Gao17Hui Yang18Binggui Sun19Rongqiao He20Weihong Song21Hongbin Han22Zhiqian Tong23Laboratory of Alzheimer's Optoelectric Therapy, Alzheimer's Disease CenterBeijing Institute for Brain Disorders, Capital Medical UniversityBeijingChinaLaboratory of Alzheimer's Optoelectric Therapy, Alzheimer's Disease CenterBeijing Institute for Brain Disorders, Capital Medical UniversityBeijingChinaDepartment of Psychiatry, Townsend Family LaboratoriesThe University of British ColumbiaVancouverCanadaSchool of Engineering, Mechanical Engineering with Renewable Energy. Old College, The University of EdinburghEdinburghUnited KingdomDepartment of RadiologyPeking University Third Hospital, Key Laboratory of Magnetic Resonance Imaging Equipment and TechniqueBeijingChinaDepartment of RadiologyPeking University Third Hospital, Key Laboratory of Magnetic Resonance Imaging Equipment and TechniqueBeijingChinaDepartment of RadiologyPeking University Third Hospital, Key Laboratory of Magnetic Resonance Imaging Equipment and TechniqueBeijingChinaDepartment of RadiologyPeking University Third Hospital, Key Laboratory of Magnetic Resonance Imaging Equipment and TechniqueBeijingChinaLaboratory of Alzheimer's Optoelectric Therapy, Alzheimer's Disease CenterBeijing Institute for Brain Disorders, Capital Medical UniversityBeijingChinaLaboratory of Alzheimer's Optoelectric Therapy, Alzheimer's Disease CenterBeijing Institute for Brain Disorders, Capital Medical UniversityBeijingChinaLaboratory of Alzheimer's Optoelectric Therapy, Alzheimer's Disease CenterBeijing Institute for Brain Disorders, Capital Medical UniversityBeijingChinaCentral Laboratory, Shantou University Medical CollegeGuangdongChinaCentral Laboratory, Shantou University Medical CollegeGuangdongChinaCentral Laboratory, Shantou University Medical CollegeGuangdongChinaSection of Environmental BiomedicineHubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal UniversityWuhanChinaSection of Environmental BiomedicineHubei Key Laboratory of Genetic Regulation and Integrative Biology, College of Life Sciences, Central China Normal UniversityWuhanChinaDepartment of NeurobiologySchool of Basic Medical Sciences, Capital Medical UniversityBeijingChinaDepartment of NeurobiologySchool of Basic Medical Sciences, Capital Medical UniversityBeijingChinaDepartment of NeurobiologySchool of Basic Medical Sciences, Capital Medical UniversityBeijingChinaSchool of Basic Medical Sciences, Zhejiang UniversityHangzhouChinaLaboratory of Alzheimer's Optoelectric Therapy, Alzheimer's Disease CenterBeijing Institute for Brain Disorders, Capital Medical UniversityBeijingChinaDepartment of Psychiatry, Townsend Family LaboratoriesThe University of British ColumbiaVancouverCanadaDepartment of RadiologyPeking University Third Hospital, Key Laboratory of Magnetic Resonance Imaging Equipment and TechniqueBeijingChinaLaboratory of Alzheimer's Optoelectric Therapy, Alzheimer's Disease CenterBeijing Institute for Brain Disorders, Capital Medical UniversityBeijingChinaAbstract 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.https://doi.org/10.1016/j.trci.2019.09.007Red light (RL)Alzheimer's disease (AD)Amyloid β (Aβ)Formaldehyde (FA)Formaldehyde dehydrogenase (FDH)Extracellular space (ECS) |
| spellingShingle | Xiangpei Yue Yufei Mei Yun Zhang Zheng Tong Dehua Cui Jun Yang Aibo Wang Rui Wang Xuechao Fei Li Ai Yalan Di Hongjun Luo Hui Li Wenhong Luo Yu Lu Rui Li Chunli Duan Ge Gao Hui Yang Binggui Sun Rongqiao He Weihong Song Hongbin Han Zhiqian Tong New insight into Alzheimer's disease: Light reverses Aβ‐obstructed interstitial fluid flow and ameliorates memory decline in APP/PS1 mice Alzheimer’s & Dementia: Translational Research & Clinical Interventions Red light (RL) Alzheimer's disease (AD) Amyloid β (Aβ) Formaldehyde (FA) Formaldehyde dehydrogenase (FDH) Extracellular space (ECS) |
| 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 | Red light (RL) Alzheimer's disease (AD) Amyloid β (Aβ) Formaldehyde (FA) Formaldehyde dehydrogenase (FDH) Extracellular space (ECS) |
| url | https://doi.org/10.1016/j.trci.2019.09.007 |
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