# Synergistic effects of surface-enhanced Raman spectroscopy and enzyme-linked immunoassays in diagnosis of Alzheimer's disease, mild cognitive impairment, and late-life depression

**Authors:** Xi Mei, Zheng Zhao, Juan Wang, Conglong Qiu, Longhui Li, Changchun Xiong, Shanshan Zhu, Chengying Zheng

PMC · DOI: 10.3389/fneur.2025.1615457 · Frontiers in Neurology · 2025-07-02

## TL;DR

This study shows that combining two blood-based tests can improve the accuracy of diagnosing Alzheimer's disease, mild cognitive impairment, and late-life depression.

## Contribution

The novel contribution is demonstrating the synergistic diagnostic performance of combining SERS and ELISA for neurodegenerative and neuropsychiatric disorders.

## Key findings

- SERS and ELISA biomarkers significantly differed among Alzheimer's, MCI, LLD, and control groups.
- Combining SERS and ELISA improved diagnostic accuracy compared to using either method alone.
- Key SERS peaks and ELISA biomarkers showed significant differences with p-values under 0.05.

## Abstract

Objective tests that can be used to identify neurodegenerative diseases and neuropsychiatric disorders are urgently needed. The primary objective of this study is to evaluate the diagnostic accuracy of surface-enhanced Raman spectroscopy (SERS), a novel blood-based detection method, in differentiating neurodegenerative diseases and neuropsychiatric disorders. Additionally, we aim to assess the synergistic diagnostic performance of combining SERS with enzyme-linked immunosorbent assay (ELISA) technology for Alzheimer's disease (AD), mild cognitive impairment (MCI), and late-life depression (LLD).

In total, 23 patients with AD, 24 with MCI, 20 with LLD, and 20 cognitively normal (control) individuals were enrolled. ELISA and SERS were used to test various biomarkers in the AD, MCI, LLD, and control groups.

Amyloid-β, tau, brain-derived neurotrophic factor, proinflammatory cytokine IL-1β, and growth differentiation factor-15 levels as measured using ELISA significantly differed among the four groups (P < 0.05). SERS peaks at 592 (P = 0.038), 725 (P = 0.001), 1,003 (P = 0.010), 1,331 (P = 0.000), and 165 cm−1 (P = 0.000) likewise significantly differed among the four groups. The area under the curve was significantly higher after combining multiple blood indicators than that with single-blood indicators.

Combining SERS and ELISA can significantly increase diagnostic accuracy for AD, MCI, and LLD. The findings are expected to provide potential therapeutic targets for precise intervention in these diseases, thereby contributing to improved clinical stratification and personalized treatment strategies.

ChiCTR2300076307 (30/09/2023).

## Linked entities

- **Proteins:** MAPT (microtubule associated protein tau), IL1B (interleukin 1 beta)
- **Diseases:** Alzheimer's disease (MONDO:0004975)

## Full-text entities

- **Genes:** APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, BDNF (brain derived neurotrophic factor) [NCBI Gene 627] {aka ANON2, BULN2}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, GDF15 (growth differentiation factor 15) [NCBI Gene 9518] {aka GDF-15, HG, MIC-1, MIC1, NAG-1, PDF}
- **Diseases:** MCI (MESH:D060825), AD (MESH:D000544), LLD (MESH:D003866), neuropsychiatric disorders (MESH:D001523), neurodegenerative diseases (MESH:D019636)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12263916/full.md

## References

56 references — full list in the complete paper: https://tomesphere.com/paper/PMC12263916/full.md

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Source: https://tomesphere.com/paper/PMC12263916