Label-Free SERS Strategy for In Situ Monitoring and Real-Time Imaging of Aβ Aggregation Process in Live Neurons and Brain Tissues

The aggregation of Aβ has been reported to closely correlate with Alzheimer’s disease (AD). However, clear monitoring of the entire aggregation process of Aβ from monomer to fibril has been scarcely reported until now. Herein, we developed a label-free ratiometric surface enhanced Raman spectroscopic (SERS) platform for real-time monitoring of the entire process of Aβ aggregation in neurons and brain tissues. Different gold nanoparticles, generated in situ with Aβ monomer and fibril as templates separately, were served as effective SERS substrates to achieve a high sensitivity with a limit of detection (LOD) down to 70 ± 4 pM and 3.0 ± 0.5 pM for Aβ40 monomer and fibrils, respectively. Besides, the introduction of ratiometric determination of Aβ monomer and fibril (I1244/I1268) realized real-time monitoring of the entire aggregation process of Aβ monomer with high accuracy and selectivity against other proteins and amino acids. The significant analytical performance of the developed platform, together with good biocompatibility, long-term stability, and remarkable spatial resolution, enabled the present SERS platform imaging and real-time monitoring and imaging of Aβ aggregation influenced by different metal ions (Cu2+, Zn2+, and Fe3+) in neurons and brain tissues at the single cell level. Our results suggested that Cu2+ and Zn2+ ion of low concentration (10 μM) promoted fibril formation, while Fe3+ and Zn2+ of high concentration (100 μM) showed inhibition of fibrosis.