Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer's disease continuum
Goossens, Julie (ADx NeuroSciences NV)
Cervantes González, Alba (Institut d'Investigació Biomèdica Sant Pau)
Dewit, Nele (Medpace Reference Laboratories (A.A.))
Lidón Gil, Laia (Institut d'Investigació Biomèdica Sant Pau)
Fortea, Juan (Institut d'Investigació Biomèdica Sant Pau)
Alcolea, Daniel (Institut d'Investigació Biomèdica Sant Pau)
Lleó, Alberto (Institut d'Investigació Biomèdica Sant Pau)
Belbin, Olivia (Institut d'Investigació Biomèdica Sant Pau)
Vanmechelen, Eugeen (ADx NeuroSciences NV)
Universitat Autònoma de Barcelona

Data:	2023
Resum:	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 tests, spearman correlation, and ANCOVA analyses. 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 = 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 = 0. 04 to 0. 19, p < 0. 05). Our novel digital immunoassay accurately measures VAMP-2 changes in CSF, which reflect AD biomarkers and cognitive performance across multiple domains.
Ajuts:	Instituto de Salud Carlos III DTS-22/00111 Instituto de Salud Carlos III PI18/00327 Instituto de Salud Carlos III PI18/00435
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Alzheimer's disease ; Biomarker ; Cerebrospinal fluid ; Cognitive domains ; Neurogranin ; SNAP-25 ; Synapse ; VAMP-2
Publicat a:	Alzheimer's research & therapy, Vol. 15 Núm. 1 (december 2023) , p. 186, ISSN 1758-9193

DOI: 10.1186/s13195-023-01336-0
PMID: 37898760

13 p, 3.5 MB

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Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Recerca Sant Pau
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