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 A beta has been reported to closely correlate with Alzheimer's disease (AD). However, clear monitoring of the entire aggregation process of A beta 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 A beta aggregation in neurons and brain tissues. Different gold nano-particles, generated in situ with A beta 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 A beta(40) monomer and fibrils, respectively. Besides, the introduction of ratiometric determination of A beta monomer and fibril (I-1244/I-1268) realized real-time monitoring of the entire aggregation process of A beta 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 A beta 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 mu M) promoted fibril formation, while Fe3+ and Zn2+ of high concentration (100 mu M) showed inhibition of fibrosis.