Aβ plaque-selective NIR fluorescence probe to differentiate Alzheimer's disease from tauopathies

Selective detection and staining of toxic amyloid plaques, a potential biomarker present in the Alzheimer's disease (AD) brain is crucial for both clinical diagnosis and monitoring AD disease progression. Herein, we report a coumarin-quinoline (CQ) conjugate-based turn-on near-infrared (NIR) fluorescence probe for specific detection of beta-amyloid (A beta) aggregates. CQ probe is highly sensitive and exhibits similar to 100-fold fluorescence enhancement in vitro upon binding A beta aggregates with enhanced quantum yield. Furthermore, the probe has similar to 10-fold higher binding affinity towards A beta aggregates (86 nM) compared to commonly used Thioflavin T. Most importantly, CQ probe displays unambiguous selectivity towards A beta aggregates compared to other toxic protein aggregates such as tau, alpha-synuclein (alpha-Syn) and islet amyloid polypeptide (IAPP). In addition, CQ is nontoxic to neuronal cells and shows significant blood brain barrier permeability. Remarkably, CQ stains A beta plaques in human brain tissue over co-existing tau aggregates and neurofibrillary tangles (NFTs), which are associated in AD and tauopathies. This is a highly desirable attribute to distinguish AD from tau pathology and mixed dementia.