Early-stage Alzheimer's disease profiling in blood achieved by multiplexing aptamer-SERS biosensors

Biosens Bioelectron. 2025 Jan 15:268:116907. doi: 10.1016/j.bios.2024.116907. Epub 2024 Nov 2.

Abstract

Neurological disorders are the second leading cause of death globally, with Alzheimer's disease (AD) emerging as a significant contributor, responsible for 276 million cases in disability-adjusted life years. Conventional diagnostic methods are often invasive, costly, and place a considerable strain on global healthcare systems. In this study, we presented an innovative and efficient strategy for AD assessment through blood profiling using a multiwell glass chip integrated with aptamer-based surface-enhanced Raman scattering (SERS) biosensors. High-affinity aptamers were selected using capillary electrophoresis-based systematic evolution of ligands by exponential enrichment (CE-SELEX). A mouse brain injury model was employed to systematically investigate biomarkers indicative of physiological, vascular, and cellular damage, such as neurogranin (Nrgn), angiopoietin-2 (Angio-2), PRDX3, lactate dehydrogenase (L-LDH), and τ-441, which were quantified at atto-molar levels in blood samples. Additionally, with the aid of CT-scan imaging, an aptamer-SERS assay was developed to evaluate the dynamic regulation of AD biomarkers. The aptamer-SERS biosensor system was also applied to human samples, demonstrating its capability to multiplex AD biomarkers and establish a time-dependent correlation between percentage biomarker regulation and disease progression. The innovative design, fabrication of aptamer-SERS nanoprobes, and the bio-sensing outcomes illustrate the strong potential of this approach for selective, sensitive, and quantitative early-stage AD diagnosis in clinical applications.

Keywords: Alzheimer’s disease (AD); Aptamer; Biosensors; Capillary-electrophoresis based systematic evolution of ligands by exponential enrichment (CE-SELEX); Nanoprobes; Surface-enhanced Raman scattering (SERS).

MeSH terms

  • Alzheimer Disease* / blood
  • Alzheimer Disease* / diagnosis
  • Animals
  • Aptamers, Nucleotide* / chemistry
  • Biomarkers* / blood
  • Biosensing Techniques* / instrumentation
  • Biosensing Techniques* / methods
  • Humans
  • Mice
  • SELEX Aptamer Technique
  • Spectrum Analysis, Raman / methods

Substances

  • Aptamers, Nucleotide
  • Biomarkers