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

Biosens Bioelectron. 2019 Oct 1:142:111518. doi: 10.1016/j.bios.2019.111518. Epub 2019 Jul 15.

Abstract

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.

Keywords: Alzheimer's disease; Quantitative detection; Ratiometric fluorescence probe; Soluble Aβ; Zn(2+)-mediated recognition.

MeSH terms

  • Alzheimer Disease / blood
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnosis
  • Amyloid beta-Peptides / analysis*
  • Amyloid beta-Peptides / blood
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Biosensing Techniques / methods*
  • Cations, Divalent / chemistry
  • Chelating Agents / chemistry*
  • Fluorescent Dyes / chemistry*
  • Humans
  • Naphthalenes / chemistry*
  • Spectrometry, Fluorescence / methods
  • Zinc / chemistry

Substances

  • Amyloid beta-Peptides
  • Cations, Divalent
  • Chelating Agents
  • Fluorescent Dyes
  • Naphthalenes
  • Zinc