Work

Visualizing and mapping Aβ plaques by curcumin-derived NIR sensors: Multitarget theranostic agents for Alzheimer's disease

Year: 2026

Type: article

Abstract: Two curcumin derivatives, structurally related to the CRANAD family of compounds, were investigated for their theranostic properties in Alzheimer's disease. They exhibited fluorescence emission in the NIR region (650–690 nm) with a significant Stokes' shift (70–90 nm). Their affinity for Aβ aggregates, oligomers and monomers allows to detect, differentiate and map in vitro the various amyloid species within and around the plaques by fluorescence microscopy. Fluorescence lifetime microscopy, a robust and sensitive technique allowing to visualize biomolecules with high spatial resolution at nanomolar level, was employed to discriminate the less soluble and more toxic species from the more soluble ones by determination of fluorescence lifetime values at the core and the periphery of the β-amyloid plaques, without the need for the use of antibodies. In vivo brain images show that the fluorescence signals of the sensors are 5–6 times higher for transgenic mice with aberrant proteins than wild type mice after intraperitoneal injection, differentiating plaques of amyloid beta (Aβ) protein in real samples in vivo . These experiments also showed a good blood brain barrier penetration of the sensors, which remain in the brain for 90–120 min, opening up the possibility of their therapeutic use. In vitro studies showed a good activity of both compounds as inhibitors of Aβ aggregation into small soluble oligomers and large insoluble aggregates and also the inhibition of tau protein aggregation, both in a dose-dependent manner. These studies confirm that both compounds have an unprecedented profile that justifies their further study as small-molecule theranostic agents in AD. • Differentiation between amyloid oligomers and aggregates by spectroscopic changes. • Detection of amyloid species in AD mice in vivo by optical imaging. • Mapping the different amyloid species within and around amyloid plaques. • Highly detailed view of amyloid plaques without the need for antibodies. • Antiaggregating activity against amyloid beta and tau proteins in vitro .

Source: Bioorganic Chemistry

DOI: 10.1016/j.bioorg.2026.109559

Authors: Álvaro Sarabia-Vallejo, José Clerigué, M. Antonia Martín, Pilar López-Alvarado, Chongzhao Ran, J. Carlos Menéndez