Early onset diagnosis in Alzheimer’s disease patients via amyloid-β oligomers-sensing probe in cerebrospinal fluid

• Published in: Nature communications 2024-02, Vol.15 (1), p.1004-1004, Article 1004
• Main Authors: An, Jusung, Kim, Kyeonghwan, Lim, Ho Jae, Kim, Hye Yun, Shin, Jinwoo, Park, InWook, Cho, Illhwan, Kim, Hyeong Yun, Kim, Sunghoon, McLean, Catriona, Choi, Kyu Yeong, Kim, YoungSoo, Lee, Kun Ho, Kim, Jong Seung
• Format: Article
• Language: English
• Subjects: 119/118; 14/34; 140/131; 140/58; 147/143; 631/92/96; 639/638/11/874; 692/53/2421; 692/699/375/365/1283; 692/700/139/1420; 9/10; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Amyloidogenic Proteins; Biomarkers - cerebrospinal fluid; Cerebrospinal fluid; Cognitive ability; Cognitive Dysfunction; Curcumin; Dementia disorders; Diagnosis; Fibrillogenesis; Fluorescent indicators; Humanities and Social Sciences; Humans; Hydrophobicity; multidisciplinary; Neurodegenerative diseases; Oligomerization; Oligomers; Patients; Peptide Fragments - cerebrospinal fluid; Quinoline; Science; Science (multidisciplinary); Self-assembly; tau Proteins - cerebrospinal fluid; β-Amyloid
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-44818-x

Amyloid-β (Aβ) oligomers are implicated in the onset of Alzheimer’s disease (AD). Herein, quinoline-derived half-curcumin-dioxaborine (Q-OB) fluorescent probe was designed for detecting Aβ oligomers by finely tailoring the hydrophobicity of the biannulate donor motifs in donor-π-acceptor structure. Q-OB shows a great sensing potency in dynamically monitoring oligomerization of Aβ during amyloid fibrillogenesis in vitro. In addition, we applied this strategy to fluorometrically analyze Aβ self-assembly kinetics in the cerebrospinal fluids (CSF) of AD patients. The fluorescence intensity of Q-OB in AD patients’ CSF revealed a marked change of log ( I / I 0 ) 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 for early diagnosis of AD. 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. In this work, the authors characterize a small molecule fluorescent probe pioneering early diagnosis of Alzheimer’s disease through identification of amyloid-β oligomers in patients’ cerebrospinal fluid, demonstrating potential for clinical application.