A simple approach to quantitative determination of soluble amyloid-beta peptides using a ratiometric fluorescence probe

摘要

Alzheimer's disease (AD) is a progressive neurodegenerative illness that affects the elderly population worldwide. The definite diagnosis of AD still depends on post-mortem pathological examination of amyloid plaques consisting of amyliod-beta peptides (A beta) fibrils in the brain so far. However, these fibrils are not closely linked to the development of the disease. Alternatively, soluble A beta are believed to be more reliable biomarkers for early diagnosis of AD. Here, we report a simple approach to quantitative detection of soluble A beta species using N-(6-(benzothiazol-2-yl)pyridin-3-yl)-5-(dimethylamino)naphthalene-1-sulfonamide (BPNS) as a ratiometric fluorescence Zn2+ probe. This ratiometric fluorescence assay is based on the competition of soluble A beta with BPNS for Zn2+, that is, soluble A beta species with higher chelation affinity can capture Zn2+ from BPNS-Zn2+ adduct, thereby reactivating the ratiometric fluorescence response of BPNS. BPNS exhibited perfect linear relationship (R-2 = 0.998) in accordance with the concentration of soluble A beta in the presence of Zn (2+). The assay possesses strong anti-interference capacity against exogenous agent or the other proteins, thanks to the high selectivity for soluble A beta species. Importantly, this assay can quantitatively detect soluble A beta species from different types of biological fluids, such as artificial cerebrospinal fluid (ACSF), serum, and plasma in half an hour. This assay provides a low-cost, fast, sensitive, and simple approach for quantitative detection of soluble A beta species and may serve as a potential tool for early-stage AD diagnosis.