Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer’s disease continuum
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Le résumé fourni par la source
Abstract 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 2 tests, spearman correlation, and ANCOVA analyses. 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 2 = 0.62 to 0.78, p < 0.001). All three synaptic proteins were associated with all cognitive domains in individuals on the AD continuum (adj. r 2 = 0.04 to 0.19, p < 0.05). Conclusions Our novel digital immunoassay accurately measures VAMP-2 changes in CSF, which reflect AD biomarkers and cognitive performance across multiple domains.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer’s disease continuum
- Date Crossref
- 28/10/2023
- Éditeur
- Springer Science and Business Media LLC
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Ablynx (Belgium) pays non établi dans la noticeEntreprise
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ADx NeuroSciences pays non établi dans la noticeEntreprise
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Universitat Autònoma de Barcelona pays non établi dans la noticeUniversité ou école supérieure
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Hospital de Sant Pau pays non établi dans la noticeÉtablissement de santé
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Biomedical Research Networking Center on Neurodegenerative Diseases pays non établi dans la noticeStructure de recherche
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Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED) pays non établi dans la noticeInstitution
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Hospital de La Santa Creu I Sant Pau Neurology Department and IIB-Sant Pau pays non établi dans la noticeÉtablissement de santé
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Medpace Reference Laboratories (A.A.) pays non établi dans la noticeInstitution
Ablynx (Belgium), ADx NeuroSciences et Universitat Autònoma de Barcelona, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.