# Synthesis and characterization of miniaturized aptamer-based monolithic sorbent for selective extraction of β-amyloid peptides from cerebrospinal fluid

## TL;DR

Researchers created a miniaturized sorbent to selectively extract beta-amyloid peptides from cerebrospinal fluid, improving Alzheimer's disease biomarker detection.

## Contribution

A novel miniaturized aptamer-based monolithic sorbent was developed for selective extraction of Aβ peptides from complex biological samples.

## Key findings

- The mOS achieved grafting yields over 90% with high aptamer density and capacity.
- Extraction recoveries of 74% for Aβ40 and 31% for Aβ42 were achieved in artificial CSF.
- The method enabled reliable trace-level analysis with low limits of quantification and acceptable precision and accuracy.

## Abstract

The ratio between beta-amyloid (Aβ) peptides 40 and 42 is recognized as a biomarker for Alzheimer's disease, playing a significant role in early diagnosis and disease progression monitoring. Aβ peptides are present at trace levels in cerebrospinal fluid, therefore, developing a new selective extraction procedure is essential for isolating targeted biomarkers from the matrix interferents, ensuring accurate identification and quantification. In this study, a hybrid organic-silica monolith was synthesized in a 530 µm inner diameter-capillary and used for the covalent grafting of beta amyloid peptide aptamers. The resulting miniaturized oligosorbent (mOS) was applied to selectively extract Aβ peptides 40 and 42 from artificial cerebrospinal fluid (CSF) samples. The immobilization procedure achieved grafting yields higher than 90% leading to a dense coverage of Aβ aptamers (655 + 15 pmol.µL−1 of oligosorbent, n = 3, RSD = 2.3), and in a capacity exceeding 50 pmol.µL−1 of mOS. After optimization in pure media, an extraction recovery of 74% and 31% for Aβ40 and Aβ42 peptides, respectively was reached on this mOS. The developed method including extraction on mOS and LC–MS analysis achieved LLOQ values of 0.1 ng.mL−1, precision and accuracy with CV and RSD values ranging from 1.0% to 12.9% and −4.7% to 11.1%, respectively. This method was successfully applied to selectively extract Aβ peptides from artificial CSF samples, effectively isolating the two Aβ targeted peptides from this complex biological fluid and enhancing trace-level analysis reliability.

The online version contains supplementary material available at 10.1007/s00216-025-06085-7.