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Aβ-Aggregation-Generated Blue Autofluorescence Illuminates Senile Plaques as well as Complex Blood and Vascular Pathologies in Alzheimer’s Disease

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Abstract

Senile plaque blue autofluorescence was discovered around 40 years ago, however, its impact on Alzheimer’s disease (AD) pathology has not been fully examined. We analyzed senile plaques with immunohistochemistry and fluorescence imaging on AD brain sections and also Aβ aggregation in vitro. In DAPI or Hoechst staining, the nuclear blue fluorescence could only be correctly assigned after subtracting the blue plaque autofluorescence. The flower-like structures wrapping dense-core blue fluorescence formed by cathepsin D staining could not be considered central-nucleated neurons with defective lysosomes since there was no nuclear staining in the plaque core when the blue autofluorescence was subtracted. Both Aβ self-oligomers and Aβ/hemoglobin heterocomplexes generated blue autofluorescence. The Aβ amyloid blue autofluorescence not only labels senile plaques but also illustrates red cell aggregation, hemolysis, cerebral amyloid angiopathy, vascular plaques, vascular adhesions, and microaneurysms. In summary, we conclude that Aβ-aggregation-generated blue autofluorescence is an excellent multi-amyloidosis marker in Alzheimer’s disease.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (81472235), the Shanghai Jiao Tong University Medical and Engineering Project (YG2021QN53, YG2017MS71), the International Cooperation Project of National Natural Science Foundation of China (82020108017), and the Innovation Group Project of National Natural Science Foundation of China (81921002). We want to thank Dr. Ma Chao and Dr. Qiu Wenying for providing AD tissue sections from the National Human Brain Bank for Development and Function, Chinese Academy of Medical Sciences, and Peking Union Medical College, Beijing, China. In addition, we thank Housheng Wang, Pingxin Liu, Xiaoyi Bao, and Jun Wang for their excellent lab assistance.

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Authors and Affiliations

  1. Institute of Nano Biomedicine and Engineering, School of Sensing Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China

    Hualin Fu, Jilong Li, Chunlei Zhang, Guo Gao & Daxiang Cui

  2. Institute of Marine Equipment, Shanghai Jiao Tong University, Shanghai, 200240, China

    Hualin Fu & Qiqi Ge

  3. National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240, China

    Hualin Fu, Chunlei Zhang, Guo Gao & Daxiang Cui

  4. Department of Colorectal Surgery, School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai, 200092, China

    Peng Du

  5. Department of Automation, Shanghai Jiao Tong University, Shanghai, 200240, China

    Qiqi Ge & Xinping Guan

  6. The Key Laboratory of System Control and Information Processing, Ministry of Education, Shanghai, 200240, China

    Xinping Guan

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  1. Hualin Fu
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Correspondence to Hualin Fu.

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Fu, H., Li, J., Zhang, C. et al. Aβ-Aggregation-Generated Blue Autofluorescence Illuminates Senile Plaques as well as Complex Blood and Vascular Pathologies in Alzheimer’s Disease. Neurosci. Bull. (2024). https://doi.org/10.1007/s12264-023-01175-x

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