Pioneering the Early Diagnosis of Alzheimer’s Disease: Aβ Oligomers-Sensing Probe for Cerebrospinal Fluid Analysis in Patients

Abstract

Amyloid-β oligomers (oAβ) are implicated in the onset of Alzheimer’s disease (AD). Herein, quinoline-derived half-curcumin-dioxaborine (Q-OB), a highly selective and sensitive fluorescent probe, was designed for detecting oAβ by finely tailoring the amphiphilicity of the biannulate donor motifs in D-π-A structure. Q-OB shows a great sensing potency in dynamically monitoring oAβ during amyloid fibrillogenesis in vitro and in vivo. For the first time, we applied this strategy to fluorometrically analyze Aβ self-assembly kinetics in the cerebrospinal fluid (CSF) of AD patients. The fluorescence intensity of Q-OB in AD patients’ CSF revealed a marked change of log (I/I0) value of 0.34 ± 0.13 (cognitive normal), 0.15 ± 0.12 (mild cognitive impairment), and 0.14 ± 0.10 (AD dementia), guiding to distinguish a state of AD continuum. These studies demonstrate the potential of our approach can expand the currently available preclinical diagnostic platform for the early stages of AD, aiding in the disruption of pathological progression and the development of appropriate treatment strategies.