Quantification of SNAP-25 with mass spectrometry and Simoa: a method comparison in Alzheimer's disease

Johanna Nilsson; Nicholas J Ashton; Andrea L Benedet; Laia Montoliu-Gaya; Johan Gobom; Tharick A Pascoal; Mira Chamoun; Erik Portelius; Andreas Jeromin; Muriel Mendes; Henrik Zetterberg; Pedro Rosa-Neto; Ann Brinkmalm; Kaj Blennow

doi:10.1186/s13195-022-01021-8

Quantification of SNAP-25 with mass spectrometry and Simoa: a method comparison in Alzheimer's disease

Alzheimers Res Ther. 2022 Jun 4;14(1):78. doi: 10.1186/s13195-022-01021-8.

Authors

Johanna Nilsson¹, Nicholas J Ashton^{2

3

4

5}, Andrea L Benedet^{2

6

7}, Laia Montoliu-Gaya², Johan Gobom^{2

8}, Tharick A Pascoal^{6

7}, Mira Chamoun^{6

7}, Erik Portelius⁸, Andreas Jeromin⁹, Muriel Mendes⁹, Henrik Zetterberg^{2

8

10

11

12}, Pedro Rosa-Neto^{6

7

13}, Ann Brinkmalm^{2

8}, Kaj Blennow^{2

8}

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, SE-43180 Mölndal, Gothenburg, Sweden. Johanna.nilsson.4@gu.se.
² Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg, SE-43180 Mölndal, Gothenburg, Sweden.
³ Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.
⁴ Department of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.
⁵ NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK.
⁶ Translational Neuroimaging Laboratory, McGill University Research Centre for Studies in Aging, Alzheimer's Disease Research Unit, Douglas Research Institute, Le Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l'Ouest-de-l'Île-de-Montréal, Montreal, Canada.
⁷ Department of Neurology and Neurosurgery, Psychiatry and Pharmacology and Therapeutics, McGill University, Montréal, Canada.
⁸ Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, SE-43180, Mölndal, Sweden.
⁹ Quanterix. Corp, Billerica, MA, USA.
¹⁰ UK Dementia Research Institute at UCL, London, UK.
¹¹ Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK.
¹² Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
¹³ Montreal Neurological Institute, Montréal, QC, Canada.

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 (r_s) > 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.

Keywords: Alzheimer’s disease; Biomarkers; Mass spectrometry; SNAP-25; Synaptic pathology.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Alzheimer Disease* / cerebrospinal fluid
Amyloid beta-Peptides / cerebrospinal fluid
Biomarkers / cerebrospinal fluid
Cognitive Dysfunction*
Humans
Mass Spectrometry
Peptide Fragments / cerebrospinal fluid
Synaptosomal-Associated Protein 25 / cerebrospinal fluid
tau Proteins / cerebrospinal fluid

Substances

Amyloid beta-Peptides
Biomarkers
Peptide Fragments
Synaptosomal-Associated Protein 25
tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding