Detecting Alzheimer’s disease early remains challenging, as current methods require invasive procedures or expensive centralized equipment unsuitable for widespread screening. Researchers at the University of Naples Federico II have developed a cost-effective electrochemical sensor that detects beta-amyloid peptides directly in blood plasma, potentially bringing point-of-care Alzheimer’s screening closer to reality. The team published their findings in Biosensors and Bioelectronics: X in September 2025, demonstrating a novel paper-based preconcentration method that significantly enhances detection sensitivity.
Key Points
- The research team developed a label-free electrochemical immunosensor coupled with a paper-based origami preconcentration device to detect Aβ(1-42), a central biomarker for Alzheimer’s pathology, with detection limits of 2.7 nanograms per milliliter (ng/mL) in buffer and 4.7 ng/mL in undiluted plasma.
- The innovative origami preconcentration technique produced up to 5-fold signal enhancement at low Aβ(1-42) concentrations, addressing the challenge of detecting extremely low biomarker levels in early-stage disease.
- The platform demonstrated satisfactory repeatability (under 10% variation) and high selectivity against interfering proteins including leptin, thrombin, and albumin.
- This pre-clinical analytical study used screen-printed electrodes combined with systematic electrochemical optimization and validated the sensor using artificially spiked plasma from healthy volunteers, with each measurement performed in quadruplicate (n=4 technical replicates), establishing proof-of-concept but requiring validation with actual patient samples containing endogenous Aβ(1-42) levels and comparison against established diagnostic standards before clinical translation.
The sensor represents progress toward accessible Alzheimer’s screening, though detection limits remain above the sub-nanogram concentrations in early-stage disease, requiring further sensitivity improvements.
The Data
- The immunosensor achieved limits of detection of 2.7 ng/mL in buffer and 4.7 ng/mL in undiluted plasma, with linear ranges from 2 to 1,000 ng/mL (R² = 0.97) and 0 to 100 ng/mL (R² = 0.98) respectively.
- When coupled with the paper-based origami preconcentration device, signal enhancement ranged from 316-394% (4-5 fold increase) at low concentrations in buffer and plasma, with p-values ranging from 0.0036 to 0.000006 in buffer and 0.032 to 0.0088 in plasma.
- Selectivity testing demonstrated negligible signal changes (up to 4%) when exposed to interfering proteins individually, and mixture testing with Aβ(1-42) plus interferents showed no significant difference from Aβ-only conditions, confirming high antibody specificity.
- The authors acknowledged a critical limitation: despite the preconcentration enhancement, detection limits remain above the 8-30 picograms per milliliter (pg/mL, or trillionths of a gram) plasma concentrations found in healthy individuals and even lower levels in early Alzheimer’s patients, necessitating further sensitivity improvements; the narrower linear range in plasma reflects matrix effects from biological components that can foul electrodes.
Industry Context
Overall, this work offers a promising foundation for the development of accessible and scalable tools for early Alzheimer’s disease screening.
Antonella Miglione and colleagues, University of Naples Federico II
This research addresses a critical gap in Alzheimer’s diagnostics by combining affordability with point-of-care potential. While cerebrospinal fluid remains the gold standard for measuring Aβ levels, its invasive collection makes it unsuitable for population screening. The FDA’s May 2025 clearance of the first blood-based Alzheimer’s diagnostic (Lumipulse® G test) validated plasma biomarker testing but still requires centralized labs.
The team’s label-free design eliminates enzymatic or fluorescent tags that complicate fabrication. The paper-based origami preconcentration device completes enrichment within one minute using only capillary action, adapting technology previously validated for nucleic acid detection.
Funded by Italian PRIN project No. 2022WN89PC with no conflicts declared, the study tested only artificially spiked samples. Clinical validation will require sub-nanogram sensitivity, detection in actual patient samples, and multicenter comparisons against PET imaging and CSF analysis.
The study, “Paper-based origami assisted and enhanced electroanalytical detection of β-Amyloid peptide in plasma samples,” was published in Biosensors and Bioelectronics: X, September 2025 (DOI: 10.1016/j.biosx.2025.100687).
