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

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-β peptides (Aβ) fibrils in the brain so far. However, these fibrils are not closely linked to the development of the disease. Alternatively, soluble Aβ are believed to be more reliable biomarkers for early diagnosis of AD. Here, we report a simple approach to quantitative detection of soluble Aβ 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 Aβ with BPNS for Zn²⁺, that is, soluble Aβ 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 (R² = 0.998) in accordance with the concentration of soluble Aβ in the presence of Zn²⁺. The assay possesses strong anti-interference capacity against exogenous agent or the other proteins, thanks to the high selectivity for soluble Aβ species. Importantly, this assay can quantitatively detect soluble Aβ 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 Aβ species and may serve as a potential tool for early-stage AD diagnosis.