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The pre-synaptic vesicle protein synaptotagmin is a novel biomarker for Alzheimer’s disease
Open accessAbstract
BACKGROUND: Synaptic degeneration is a central pathogenic event in Alzheimer's disease that occurs early during the course of disease and correlates with cognitive symptoms. The pre-synaptic vesicle protein synaptotagmin-1 appears to be essential for the maintenance of an intact synaptic transmission and cognitive function. Synaptotagmin-1 in cerebrospinal fluid is a candidate Alzheimer biomarker for synaptic dysfunction that also may correlate with cognitive decline. METHODS: In this study, a novel mass spectrometry-based assay for measurement of cerebrospinal fluid synaptotagmin-1 was developed, and was evaluated in two independent sample sets of patients and controls. Sample set I included cerebrospinal fluid samples from patients with dementia due to Alzheimer's disease (N = 17, age 52-86 years), patients with mild cognitive impairment due to Alzheimer's disease (N = 5, age 62-88 years), and controls (N = 17, age 41-82 years). Sample set II included cerebrospinal fluid samples from patients with dementia due to Alzheimer's disease (N = 24, age 52-84 years), patients with mild cognitive impairment due to Alzheimer's disease (N = 18, age 58-83 years), and controls (N = 36, age 43-80 years). RESULTS: The reproducibility of the novel method showed coefficients of variation of the measured synaptotagmin-1 peptide 215-223 (VPYSELGGK) and peptide 238-245 (HDIIGEFK) of 14 % or below. In both investigated sample sets, the CSF levels of synaptotagmin-1 were significantly increased in patients with dementia due to Alzheimer's disease (P ≤ 0.0001) and in patients with mild cognitive impairment due to Alzheimer's disease (P < 0.001). In addition, in sample set I the synaptotagmin-1 level was significantly higher in patients with mild cognitive impairment due to Alzheimer's disease compared with patients with dementia due to Alzheimer's disease (P ≤ 0.05). CONCLUSIONS: Cerebrospinal fluid synaptotagmin-1 is a promising biomarker to monitor synaptic dysfunction and degeneration in Alzheimer's disease that may be useful for clinical diagnosis, to monitor effect on synaptic integrity by novel drug candidates, and to explore pathophysiology directly in patients with Alzheimer's disease.
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“Neurogranin (a key regulator of the calcium-binding protein calmodulin), synaptogamin (a calcium sensor protein), and SNAP-25 (a component of the SNARE [soluble N-ethylmaleimide sensitive factor attachment protein receptor] complex) are the strongest candidates for in vivo tracking synaptic homeostasis (131–133).”
From The β-Secretase BACE1 in Alzheimer’s Disease (2021) · cites this paper as [131]
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Metadata
- Authors
- Öhrfelt, A., Brinkmalm, A., Dumurgier, J., Brinkmalm, G., Hansson, O., Zetterberg, H., Bouaziz-Amar, E., Hugon, J., Paquet, C., & Blennow, K.
- Affiliations
- Sahlgrenska University Hospital (SE)
- Inserm (FR)
- Lund University (SE)
- Corresponding author
- Öhrfelt, Annika
- ORCID
- Venue
- Alzheimer's Research & Therapy
- Published
- 2016-10-03
- Volume
- 8
- Issue
- 1
- Pages
- 41-41
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC5048479
- OpenAlex
- W2529693680
- Cited by
- 184
- References
- 40
- Citations by year
- 2026: 6 · 2025: 17 · 2024: 35 · 2023: 18 · 2022: 31 · 2021: 22 · 2020: 26 · 2019: 14 · 2018: 13 · 2017: 2
- FWCI
- 7.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Alzheimer s Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- Swedish Brain Power
- Swedish research council
- Swedish Alzheimer foundation
- European research council
- ALF
- The Knut and Wallenberg foundation
- Demensfonden
- Eivind och Elsa K:son Sylvans stiftelse
- the Wolfson foundation
- Märtha och Gustaf Ågrens stiftelse
- Gun och Bertil Stohnes Stiftelse
- Stiftelsen gamla tjänarinnor
- Magnus Bergvalls Stiftelse
- Svenska Läkaresällskapet
- Åhlén-stiftelsen
- BMBF BIOMARK-APD
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- synaptotagmin-1, Alzheimer's disease, cerebrospinal fluid biomarkers, synaptic dysfunction, synaptic degeneration, mild cognitive impairment, dementia, cognitive decline, drug monitoring, neurodegeneration biomarkers, tau protein, neuroinflammation, neurofibrillary tangles, neurodegeneration
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Cognition Disorders, Dementia, Female, Humans, Male, Middle Aged, Peptide Fragments, Peptides, Psychiatric Status Rating Scales, ROC Curve, Mass Spectrometry, Amyloid beta-Peptides, tau Proteins, Immunoprecipitation, Synaptotagmin I
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