Synaptosomal‐Associated Protein 25 kDA (SNAP‐25) Levels in Cerebrospinal Fluid: Implications for Alzheimer's Disease Diagnosis and Monitoring
Synaptic degeneration has been linked to cognitive decline. The presynaptic protein, synaptosomal-associated protein 25 kDA (SNAP-25), is crucial for synaptic transmission and has been suggested as a biomarker in Alzheimer's disease (AD). In the current study, we investigated the ability of SNAP-25 to differentiate between heterogenous dementia etiologies and whether SNAP-25 could be a staging marker in AD. SNAP-25 in the cerebrospinal fluid (CSF) from a retrospective (n = 187) and a prospective (n = 134) cohort was investigated with immunoprecipitation mass spectrometry (IP-MS) and single-molecule array (Simoa), respectively. Both cohorts consisted of healthy controls (HC) and patients with cognitive decline of different etiologies. CSF SNAP-25 concentration was higher in AD and non-neurodegenerative diseases (i.e., vascular dementia) compared with controls but did not differ between AD and non-AD neurodegenerative diseases. We found a trend toward an association between SNAP-25 and disease burden when comparing HC, mild cognitive impairment due to AD, and AD. CSF SNAP-25 concentrations were strongly associated with CSF phosphorylated tau (p-tau) concentrations, thus strengthening the link between synaptic dysfunction and tau pathophysiology in AD. Our initial findings suggest that SNAP-25 may be a potential biomarker for differentiating AD from dementia due to other etiologies. However, due to the significant association between SNAP-25 and p-tau proteins, the clinical utility of SNAP-25 as a diagnostic biomarker for AD may be limited, while SNAP-25 may be useful for monitoring disease progression or treatment response.
Authors
- Christian Sandøe Musaeus (ORCID: https://orcid.org/0000-0002-6442-2910)
- Ann Brinkmalm (ORCID: https://orcid.org/0000-0002-7396-3233)
- Peter Høgh (ORCID: https://orcid.org/0000-0002-8478-8098)
- Steen Gregers Hasselbalch (ORCID: https://orcid.org/0000-0003-4750-4911)
- Helena Sophia Gleerup (ORCID: https://orcid.org/0000-0001-7470-4818)
- Anja Hviid Simonsen (ORCID: https://orcid.org/0000-0002-5461-162X)
- Lana Grötschel
- Johanna Nilsson (ORCID: https://orcid.org/0000-0002-2856-6060)
- Anne B. Walls (ORCID: https://orcid.org/0000-0002-5234-5006)
- Kaj Blennow
- Nicholas J. Ashton
- Henrik Zetterberg (ORCID: https://orcid.org/0000-0002-4671-6763)
- Sofia Hjorth Wolner
Institutions
- University of Copenhagen (DK)
- University of Science and Technology of China (CN)
- King's College London (GB)
- Stavanger University Hospital (NO)
- Sahlgrenska University Hospital (SE)
- Copenhagen University Hospital (DK)
- Rigshospitalet (DK)
- Centre for Mental Health (GB)
- Sorbonne Université (FR)
- Zealand University Hospital (DK)
- Pitié-Salpêtrière Hospital (FR)
- UK Dementia Research Institute (GB)
- National Hospital for Neurology and Neurosurgery (GB)
- Institut du Cerveau (FR)
- University College London (GB)
- University of Gothenburg (SE)
Publication Details
- Journal
- Synapse
- Published
- 2025-02-06
- DOI
- https://doi.org/10.1002/syn.70010
- Citations
- 4
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 4.66
Funders
- Alzheimer's Association
- Alzheimer's Drug Discovery Foundation
- Familjen Erling-Perssons Stiftelse
- Cure Alzheimer's Fund
- Stiftelsen för Gamla Tjänarinnor
- EU Joint Programme – Neurodegenerative Disease Research
- National Institute for Health and Care Research
- University College London
- European Commission
- Hjärnfonden
- Vetenskapsrådet
- UK Dementia Research Institute
- Olav Thon Stiftelsen
- Fondation pour la Recherche sur Alzheimer
- HORIZON EUROPE Framework Programme