Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer's disease continuum.
Alzheimer’s disease
Biomarker
Cerebrospinal fluid
Cognitive domains
Neurogranin
SNAP-25
Synapse
VAMP-2
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
28 10 2023
28 10 2023
Historique:
received:
31
05
2023
accepted:
17
10
2023
medline:
30
10
2023
pubmed:
29
10
2023
entrez:
29
10
2023
Statut:
epublish
Résumé
Synapse loss is an early event that precedes neuronal death and symptom onset and is considered the best neuropathological correlate of cognitive decline in Alzheimer's disease (AD). Vesicle-associated membrane protein 2 (VAMP-2) has emerged as a promising biomarker of AD-related synapse degeneration in cerebrospinal fluid (CSF). The aim of this study was to explore the CSF profile of VAMP-2 across the AD continuum in relation to core AD biomarkers, other synaptic proteins, neurogranin (Ng) and synaptosomal-associated Protein-25 kDa (SNAP-25) and cognitive performance. We developed a digital immunoassay on the Single Molecule Array platform to quantify VAMP-2 in CSF and used existing immunoassays to quantify Ng, SNAP-25 and core CSF AD biomarkers. The clinical study included 62 cognitively unimpaired AD biomarker-negative subjects and 152 participants across the AD continuum from the SPIN cohort (Sant Pau Initiative on Neurodegeneration). Cognitive measures of episodic, semantic, executive and visuospatial domains and global cognition were included. Statistical methods included χ The VAMP-2 assay had a good analytical performance (repeatability 8.9%, intermediate precision 10.3%). Assay antibodies detected native VAMP-2 protein in human brain homogenates. CSF concentrations of VAMP-2, neurogranin and SNAP-25 were lower in preclinical AD stage 1 compared to controls and higher at later AD stages compared to AD stage 1 and were associated with core AD biomarkers, particularly total tau (adj. r Our novel digital immunoassay accurately measures VAMP-2 changes in CSF, which reflect AD biomarkers and cognitive performance across multiple domains.
Sections du résumé
BACKGROUND
Synapse loss is an early event that precedes neuronal death and symptom onset and is considered the best neuropathological correlate of cognitive decline in Alzheimer's disease (AD). Vesicle-associated membrane protein 2 (VAMP-2) has emerged as a promising biomarker of AD-related synapse degeneration in cerebrospinal fluid (CSF). The aim of this study was to explore the CSF profile of VAMP-2 across the AD continuum in relation to core AD biomarkers, other synaptic proteins, neurogranin (Ng) and synaptosomal-associated Protein-25 kDa (SNAP-25) and cognitive performance.
METHODS
We developed a digital immunoassay on the Single Molecule Array platform to quantify VAMP-2 in CSF and used existing immunoassays to quantify Ng, SNAP-25 and core CSF AD biomarkers. The clinical study included 62 cognitively unimpaired AD biomarker-negative subjects and 152 participants across the AD continuum from the SPIN cohort (Sant Pau Initiative on Neurodegeneration). Cognitive measures of episodic, semantic, executive and visuospatial domains and global cognition were included. Statistical methods included χ
RESULTS
The VAMP-2 assay had a good analytical performance (repeatability 8.9%, intermediate precision 10.3%). Assay antibodies detected native VAMP-2 protein in human brain homogenates. CSF concentrations of VAMP-2, neurogranin and SNAP-25 were lower in preclinical AD stage 1 compared to controls and higher at later AD stages compared to AD stage 1 and were associated with core AD biomarkers, particularly total tau (adj. r
CONCLUSIONS
Our novel digital immunoassay accurately measures VAMP-2 changes in CSF, which reflect AD biomarkers and cognitive performance across multiple domains.
Identifiants
pubmed: 37898760
doi: 10.1186/s13195-023-01336-0
pii: 10.1186/s13195-023-01336-0
pmc: PMC10612328
doi:
Substances chimiques
Amyloid beta-Peptides
0
Biomarkers
0
Neurogranin
132654-77-4
tau Proteins
0
Vesicle-Associated Membrane Protein 2
0
VAMP2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
186Subventions
Organisme : Instituto de Salud Carlos III
ID : PI18/00327, PI21/00327, DTS-22/00111, PI18/00435 and INT19/00016
Organisme : Instituto de Salud Carlos III
ID : PI18/00327, PI21/00327, DTS-22/00111, PI18/00435 and INT19/00016
Organisme : Network of Centres of Excellence in Neurodegeneration
ID : COEN5025
Organisme : Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas
ID : Program 1
Organisme : Fondo Europeo de Desarrollo Regional
ID : "Una manera de hacer Europa"
Organisme : Department of Health Generalitat de Catalunya
ID : AGAUR 2019 PROD 00088
Informations de copyright
© 2023. The Author(s).
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