Fluorescence lifetime probe TZ-48 enables smartphone-based detection and staging of amyloid-β in AD mouse brains and serum

Early and definitive diagnosis of Alzheimer's disease (AD) is crucial for effective intervention, yet current methods often lack accessibility and sensitivity. The pathological aggregation of amyloid-β (Aβ) peptides into plaques is a central biomarker for AD, driving neurodegeneration and cognitive decline. There is a critical need for highly sensitive, accessible, and clinically adaptable technologies to detect Aβ in both brain tissue and biofluids, addressing the diagnostic gap in early disease staging and monitoring.

Researchers developed TZ-48, a novel fluorescence lifetime-responsive probe, to detect Aβ. They characterized its binding affinity and detection limits against Aβ fibrils (Aβf) in vitro. The probe's ability to cross the blood-brain barrier (BBB) was assessed, followed by dual-mode confocal and fluorescence lifetime imaging (FLIM) in AD mouse brains to visualize and stage Aβ burden. Furthermore, TZ-48 was used for quantitative detection of Aβ in serum to differentiate AD from healthy mice. To enhance accessibility, they created ADxFluor, a smartphone-enabled platform leveraging TZ-48's fluorescence response for rapid serum Aβ assessment.

The TZ-48 probe demonstrated strong turn-on fluorescence and distinct lifetime signatures, allowing real-time tracking of Aβ aggregation kinetics. It bound Aβf with high affinity, reporting a Kd of 41 nM, and exhibited a low detection limit of 68 nM. The probe also displayed exceptional selectivity over off-target species. Importantly, TZ-48 successfully crossed the blood-brain barrier, enabling early visualization and staging of Aβ burden through dual-mode confocal and FLIM in AD mouse brains.

TZ-48 permitted quantitative detection of Aβ in serum, effectively distinguishing AD from healthy mice, highlighting its potential for biofluid-based diagnostics. The ADxFluor smartphone platform further translated this molecular capability into an accessible, rapid, and accurate assessment of serum Aβ load.