Fluorescent Peptide Nanoparticles To Detect Amyloid-Beta Aggregation In Cerebrospinal Fluid And Serum For Alzheimer'S Disease Diagnosis And Progression Monitoring

Alzheimer's disease (AD) is associated with the accumulation of insoluble forms of amyloid-beta (A beta) in plaques in extracellular spaces, as well as in the walls of blood vessels, and aggregation of microtubule protein tau in neurofibrillary tangles in neurons. In this study, we designed and synthesized a series of fluorescent cyclic peptide nanoparticles (c-PNPs) that can be used to detect A beta aggregates in both the cerebrospinal fluid (CSF) and serum, which were obtained from healthy people and AD patients in different disease stages. Our experimental studies indicate that the fluorescence intensities and wavelengths generated from the interactions between the negatively charged c-PNPs and A beta aggregates in both the CSF and serum changed with disease status, as compared to healthy individuals. The morphological and cytotoxicity studies demonstrated a potential inhibitory effect of the negatively charged c-PNPs on amyloid fibril growth. The underlying mechanisms leading to these changes are interpreted based on the aromatic, hydrophobic, and electrostatic interactions between c-PNPs and A beta peptides. These results indicate that the c-PNPs may provide a noninvasive and sensitive method for diagnosing AD and monitoring its progression.