Systematic review of curcumin-based optical imaging for amyloid-β detection in Alzheimer's disease models

Background: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by amyloid-beta (Aβ) plaque accumulation and cognitive decline. Early and precise Aβ detection is vital for effective therapeutic intervention. Curcumin-based fluorescent probes offer high specificity, non-invasive imaging compatibility, and deep tissue penetration, making them promising tools for optical Aβ imaging. This systematic review evaluates preclinical studies on curcumin-based fluorescent probes to assess their photophysical properties, imaging capabilities, and potential applications in detecting Aβ plaques in mouse models of AD. Methods: A comprehensive literature search was performed in PubMed and ScienceDirect (2000-2024). Eligible studies were original English-language articles using curcumin-based probes for optical imaging of Aβ in Alzheimer's mouse models. Data extraction focused on imaging parameters such as binding affinity [dissociation constant (Kd)], emission wavelength, quantum yield, fluorescence enhancement, and delivery methods. Results: Thirteen preclinical studies met the inclusion criteria and were analyzed. CRANAD-102 probe showed the highest binding affinity (Kd = 7.5 nM) while CRANAD-3 achieved the most significant fluorescence intensity (39.5-fold). Emission wavelengths averaged 690 nm, with longer wavelengths facilitating deeper tissue imaging. Quantum yields ranged from 0.011 to 0.40, with the highest yield (20.31) observed in CH₂Cl₂ and effective doses averaging 2.0 mg/kg. Innovative delivery methods, such as aerosolized formulations and micelle-based probes, expanded diagnostic applications, including non-invasive retinal imaging. Conclusion: Curcumin-based fluorescent probes exhibit high specificity for Aβ aggregates, effective deep tissue imaging, and non-invasive delivery potential, making them promising tools for preclinical Alzheimer's diagnostics. However, their clinical translation requires further validation in standardized preclinical and translational studies.