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

 Hualin Fu1,2,3  · Jilong Li1  · Chunlei Zhang1,3  · Peng Du4  · Guo Gao1,3  · Qiqi Ge2,5 · Xinping Guan5,6 · Daxiang Cui1,3
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 
2 Institute of Marine Equipment, Shanghai Jiao Tong University, Shanghai 200240, China 
3 National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai 200240, China 
4 Department of Colorectal Surgery, School of Medicine, Xinhua Hospital, Shanghai Jiao Tong University, Shanghai 200092, China 
5 Department of Automation, Shanghai Jiao Tong University, Shanghai 200240, China 
6 The Key Laboratory of System Control and Information Processing, Ministry of Education, Shanghai 200240, China

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.

Keywords
Senile plaque; Blue autofuorescence; Aβ; Amyloid aggregation; Hemoglobin; Cathepsin D; Microaneurysm; Alzheimer’s disease