Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease
Near-infrared fluorescence (NIRF) molecular imaging has been widely applied to monitoring therapy of cancer and other diseases in preclinical studies; however, this technology has not been applied successfully to monitoring therapy for Alzheimer’s disease (AD). Although several NIRF probes for detec...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2016
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| Online Access: | http://hdl.handle.net/1721.1/101113 |
| _version_ | 1811091127563976704 |
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| author | Zhang, Xueli Tian, Yanli Zhang, Can Tian, Xiaoyu Ross, Alana W. Moir, Robert D. Sun, Hongbin Tanzi, Rudolph E. Moore, Anna V. Ran, Chongzhao |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Zhang, Xueli Tian, Yanli Zhang, Can Tian, Xiaoyu Ross, Alana W. Moir, Robert D. Sun, Hongbin Tanzi, Rudolph E. Moore, Anna V. Ran, Chongzhao |
| author_sort | Zhang, Xueli |
| collection | MIT |
| description | Near-infrared fluorescence (NIRF) molecular imaging has been widely applied to monitoring therapy of cancer and other diseases in preclinical studies; however, this technology has not been applied successfully to monitoring therapy for Alzheimer’s disease (AD). Although several NIRF probes for detecting amyloid beta (Aβ) species of AD have been reported, none of these probes has been used to monitor changes of Aβs during therapy. In this article, we demonstrated that CRANAD-3, a curcumin analog, is capable of detecting both soluble and insoluble Aβ species. In vivo imaging showed that the NIRF signal of CRANAD-3 from 4-mo-old transgenic AD (APP/PS1) mice was 2.29-fold higher than that from age-matched wild-type mice, indicating that CRANAD-3 is capable of detecting early molecular pathology. To verify the feasibility of CRANAD-3 for monitoring therapy, we first used the fast Aβ-lowering drug LY2811376, a well-characterized beta-amyloid cleaving enzyme-1 inhibitor, to treat APP/PS1 mice. Imaging data suggested that CRANAD-3 could monitor the decrease in Aβs after drug treatment. To validate the imaging capacity of CRANAD-3 further, we used it to monitor the therapeutic effect of CRANAD-17, a curcumin analog for inhibition of Aβ cross-linking. The imaging data indicated that the fluorescence signal in the CRANAD-17–treated group was significantly lower than that in the control group, and the result correlated with ELISA analysis of brain extraction and Aβ plaque counting. It was the first time, to our knowledge, that NIRF was used to monitor AD therapy, and we believe that our imaging technology has the potential to have a high impact on AD drug development. |
| first_indexed | 2024-09-23T14:57:26Z |
| format | Article |
| id | mit-1721.1/101113 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:57:26Z |
| publishDate | 2016 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1011132022-09-29T11:42:17Z Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease Zhang, Xueli Tian, Yanli Zhang, Can Tian, Xiaoyu Ross, Alana W. Moir, Robert D. Sun, Hongbin Tanzi, Rudolph E. Moore, Anna V. Ran, Chongzhao Harvard University--MIT Division of Health Sciences and Technology Moore, Anna V. Near-infrared fluorescence (NIRF) molecular imaging has been widely applied to monitoring therapy of cancer and other diseases in preclinical studies; however, this technology has not been applied successfully to monitoring therapy for Alzheimer’s disease (AD). Although several NIRF probes for detecting amyloid beta (Aβ) species of AD have been reported, none of these probes has been used to monitor changes of Aβs during therapy. In this article, we demonstrated that CRANAD-3, a curcumin analog, is capable of detecting both soluble and insoluble Aβ species. In vivo imaging showed that the NIRF signal of CRANAD-3 from 4-mo-old transgenic AD (APP/PS1) mice was 2.29-fold higher than that from age-matched wild-type mice, indicating that CRANAD-3 is capable of detecting early molecular pathology. To verify the feasibility of CRANAD-3 for monitoring therapy, we first used the fast Aβ-lowering drug LY2811376, a well-characterized beta-amyloid cleaving enzyme-1 inhibitor, to treat APP/PS1 mice. Imaging data suggested that CRANAD-3 could monitor the decrease in Aβs after drug treatment. To validate the imaging capacity of CRANAD-3 further, we used it to monitor the therapeutic effect of CRANAD-17, a curcumin analog for inhibition of Aβ cross-linking. The imaging data indicated that the fluorescence signal in the CRANAD-17–treated group was significantly lower than that in the control group, and the result correlated with ELISA analysis of brain extraction and Aβ plaque counting. It was the first time, to our knowledge, that NIRF was used to monitor AD therapy, and we believe that our imaging technology has the potential to have a high impact on AD drug development. 2016-02-05T13:45:32Z 2016-02-05T13:45:32Z 2015-08 2015-03 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/101113 Zhang, Xueli, Yanli Tian, Can Zhang, Xiaoyu Tian, Alana W. Ross, Robert D. Moir, Hongbin Sun, Rudolph E. Tanzi, Anna Moore, and Chongzhao Ran. “Near-Infrared Fluorescence Molecular Imaging of Amyloid Beta Species and Monitoring Therapy in Animal Models of Alzheimer’s Disease.” Proc Natl Acad Sci USA 112, no. 31 (July 21, 2015): 9734–9739. en_US http://dx.doi.org/10.1073/pnas.1505420112 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Zhang, Xueli Tian, Yanli Zhang, Can Tian, Xiaoyu Ross, Alana W. Moir, Robert D. Sun, Hongbin Tanzi, Rudolph E. Moore, Anna V. Ran, Chongzhao Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease |
| title | Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease |
| title_full | Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease |
| title_fullStr | Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease |
| title_full_unstemmed | Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease |
| title_short | Near-infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of Alzheimer’s disease |
| title_sort | near infrared fluorescence molecular imaging of amyloid beta species and monitoring therapy in animal models of alzheimer s disease |
| url | http://hdl.handle.net/1721.1/101113 |
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