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

Research Background

Alzheimer’s disease (AD) is a widespread neurodegenerative disorder globally, with senile plaques being the main pathological hallmark of AD, primarily composed of β-amyloid protein (Aβ). This study explored the blue autofluorescence of senile plaques in AD—a phenomenon discovered nearly 40 years ago but not fully investigated for its impact on AD pathology. To address this, researchers analyzed senile plaques in frontal lobe brain sections from AD patients using immunohistochemistry and fluorescence imaging techniques, and conducted in vitro studies on Aβ aggregation.

Article Information

This study was jointly conducted by the following authors: Fu Hualin, Li Jilong, Zhang Chunlei, Du Peng, Gao Guo, Ge Qiqi, Guan Xinping, and Cui Daxiang. The team is from the Institute of Nano Biomedicine and Engineering at Shanghai Jiao Tong University, the Marine Equipment Research Institute, the National Center for Translational Medicine, and other affiliated institutions. The article was submitted on July 12, 2023, accepted on October 2, 2023, and published in “Neuroscience Bulletin”.

Research Process

The study was conducted in the following steps:

a) Collection and fluorescence imaging analysis of frontal lobe brain tissue sections from AD patients. b) Labeling of senile plaques with various antibodies and observation under fluorescence microscopy. c) In vitro aggregation experiments of Aβ40 and Aβ42 separately to explore the blue autofluorescence generated during the aggregation process. d) Proteinase K digestion experiments to evaluate the sensitivity of protein aggregates to protease.

Main Results

The results showed that the blue autofluorescence of senile plaque cores was more intense than the blue fluorescence of cell nuclei labeled with traditional DAPI and Hoechst. Both Aβ self-aggregates and Aβ/hemoglobin heterocomplexes produced blue autofluorescence, indicating that Aβ aggregation directly leads to the blue autofluorescence of senile plaques. Moreover, the blue autofluorescence of Aβ amyloid not only marked senile plaques but also revealed a series of important blood and vascular amyloid pathologies, including red blood cell aggregation, hemolysis, cerebral amyloid angiopathy, vascular plaques, vascular adhesion, and microaneurysms.

Conclusions and Significance

The study concluded that the blue autofluorescence generated by Aβ aggregation is an excellent label-free indicator of various amyloid pathologies in AD. Combined with the fluorescent properties of Aβ proteins, this blue autofluorescence can serve as a sensitive, label-free, low-cost, and convenient indicator for tracking the pathogenesis of AD from early blood and vascular defects to the final stage of senile plaque formation.

Research Highlights

This study comprehensively revealed the relationship between the Aβ aggregation process and the unique blue autofluorescence of senile plaques for the first time. In addition to senile plaques in AD patient brain tissue, this autofluorescence can also reveal other complex blood and vascular pathological changes, which are important parts of AD development. The methods in this study also provide a new perspective and tool to help future more detailed studies of amyloid pathologies in AD and may guide new clinical diagnostic approaches.

Although this research has its innovations, there are still many questions to be addressed, such as the role of specific Aβ oligomer subtypes in efficiently generating blue autofluorescence, and whether this autofluorescence can be used as an effective and non-invasive AD pathway monitoring marker in clinical settings.