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

Jusung An, Kyeonghwan Kim, Ho Jae Lim, Hye Yun Kim, Jinwoo Shin, InWook Park, Illhwan Cho, Hyeong Yun Kim, Sunghoon Kim, Catriona McLean, Kyu Yeong Choi, YoungSoo Kim (), Kun Ho Lee () and Jong Seung Kim ()
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Jusung An: Korea University
Kyeonghwan Kim: Yonsei University
Ho Jae Lim: Chosun University
Hye Yun Kim: Yonsei University
Jinwoo Shin: Korea University
InWook Park: Yonsei University
Illhwan Cho: Yonsei University
Hyeong Yun Kim: Yonsei University
Sunghoon Kim: Yonsei University
Catriona McLean: The Alfred Hospital
Kyu Yeong Choi: Chosun University
YoungSoo Kim: Yonsei University
Kun Ho Lee: Chosun University
Jong Seung Kim: Korea University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract 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/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 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.

Date: 2024
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DOI: 10.1038/s41467-024-44818-x

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