Quantitative imaging of amyloid beta peptide (Aβ) in Alzheimer's brain tissue by laser ablation ICP-MS using gold nanoparticles as labels

Highlights: • Quantitative imaging of Aβ in Alzheimer's disease brain by LA-ICP-MS using gold nanoparticles as labels was proposed. • Labelling conditions, immunoreaction efficiency and calibration strategy were optimized. • The proposed strategy was compared and assessed by immunohistochemistry. • Broaden the application of metal-labeling based LA-ICP-MS for pathology research and treatment of AD disease. Quantitative imaging of amyloid beta (Aβ) in brain is of great significance for pathological study and follow-up drug development of Alzheimer's disease (AD). In this work, a method using antibody-conjugated gold nanoparticles (AuNPs) was established for quantitative imaging of Aβ peptide in the brain of AD mouse by Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Aβ antibody (Anti-Aβ) was labeled with AuNPs to form the conjugate AuNPs-Anti-Aβ which was immunoreactive with Aβ in the brain slice of mouse. Quantitative imaging of Au was acquired with homogenized brain slice matrix-matched standards as external calibrants which were made by immersing in gold standard solution with different concentrations. Furthermore, the stoichiometric ratios between metal conjugates and Aβ were optimized, and the immunoreaction efficiency after labeling was also investigated. According to the molar relationship between AuNPs and Anti-Aβ (1:4.3) and the ratio of Anti-Aβ to Aβ (1:1), quantitative imaging of Aβ in brain was accomplished. The method intuitively displayed the location and concentration of Aβ aggregation, which was consistent with traditional immunohistochemical staining. Since the numerous gold atoms contained in AuNPs can enhance the signal of Aβ, the method is more intuitive and sensitive. The proposed methodology is potential in investigating the quantitative imaging of biomarker heterogeneity, and is useful to understand such complex brain mechanisms in the future.