Nilsson, Johanna;
Ashton, Nicholas J;
Benedet, Andrea L;
Montoliu-Gaya, Laia;
Gobom, Johan;
Pascoal, Tharick A;
Chamoun, Mira;
... Blennow, Kaj; + view all
(2022)
Quantification of SNAP-25 with mass spectrometry and Simoa: a method comparison in Alzheimer's disease.
Alzheimer's Research & Therapy
, 14
(1)
, Article 78. 10.1186/s13195-022-01021-8.
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Abstract
BACKGROUND: Synaptic dysfunction and degeneration are central to Alzheimer's disease (AD) and have been found to correlate strongly with cognitive decline. Thus, studying cerebrospinal fluid (CSF) biomarkers reflecting synaptic degeneration, such as the presynaptic protein synaptosomal-associated protein 25 (SNAP-25), is of importance to better understand the AD pathophysiology. METHODS: We compared a newly developed Single molecule array (Simoa) immunoassay for SNAP-25 with an in-house immunoprecipitation mass spectrometry (IP-MS) method in a well-characterized clinical cohort (n = 70) consisting of cognitively unimpaired (CU) and cognitively impaired (CI) individuals with and without Aβ pathology (Aβ+ and Aβ-). RESULTS: A strong correlation (Spearman's rank correlation coefficient (rs) > 0.88; p < 0.0001) was found between the Simoa and IP-MS methods, and no statistically significant difference was found for their clinical performance to identify AD pathophysiology in the form of Aβ pathology. Increased CSF SNAP-25 levels in CI Aβ+ compared with CU Aβ- (Simoa, p ≤ 0.01; IP-MS, p ≤ 0.05) and CI Aβ- (Simoa, p ≤ 0.01; IP-MS, p ≤ 0.05) were observed. In independent blood samples (n = 32), the Simoa SNAP-25 assay was found to lack analytical sensitivity for quantification of SNAP-25 in plasma. CONCLUSIONS: These results indicate that the Simoa SNAP-25 method can be used interchangeably with the IP-MS method for the quantification of SNAP-25 in CSF. Additionally, these results confirm that CSF SNAP-25 is increased in relation to amyloid pathology in the AD continuum.
| Type: | Article |
|---|---|
| Title: | Quantification of SNAP-25 with mass spectrometry and Simoa: a method comparison in Alzheimer's disease |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1186/s13195-022-01021-8 |
| Publisher version: | https://doi.org/10.1186/s13195-022-01021-8 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| Keywords: | Alzheimer’s disease, Biomarkers, Mass spectrometry, SNAP-25, Synaptic pathology, Alzheimer Disease, Amyloid beta-Peptides, Biomarkers, Cognitive Dysfunction, Copper, Humans, Mass Spectrometry, Peptide Fragments, Synaptosomal-Associated Protein 25, tau Proteins |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10150502 |
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