Evaluation of cerebrospinal fluid levels of synaptic vesicle protein, VAMP-2, across the sporadic Alzheimer's disease continuum.

Autor: Goossens J; ADx NeuroSciences NV, Zwijnaarde, Ghent, Belgium., Cervantes González A; Sant Pau Memory Unit, Neurology Department and IIB-Sant Pau, Hospital de La Santa Creu I Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Dewit N; Medpace Reference Laboratories (A.A.), Flow Cytometry Unit, Louvain, Belgium., Lidón L; Sant Pau Memory Unit, Neurology Department and IIB-Sant Pau, Hospital de La Santa Creu I Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Fortea J; Sant Pau Memory Unit, Neurology Department and IIB-Sant Pau, Hospital de La Santa Creu I Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Alcolea D; Sant Pau Memory Unit, Neurology Department and IIB-Sant Pau, Hospital de La Santa Creu I Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Lleó A; Sant Pau Memory Unit, Neurology Department and IIB-Sant Pau, Hospital de La Santa Creu I Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain., Belbin O; Sant Pau Memory Unit, Neurology Department and IIB-Sant Pau, Hospital de La Santa Creu I Sant Pau, Universitat Autonoma de Barcelona, Barcelona, Spain. obelbin@santpau.cat.; Network Center for Biomedical Research in Neurodegenerative Diseases (CIBERNED), Madrid, Spain. obelbin@santpau.cat., Vanmechelen E; ADx NeuroSciences NV, Zwijnaarde, Ghent, Belgium. Eugeen.Vanmechelen@adxneurosciences.com.
Jazyk: angličtina
Zdroj: Alzheimer's research & therapy [Alzheimers Res Ther] 2023 Oct 28; Vol. 15 (1), pp. 186. Date of Electronic Publication: 2023 Oct 28.
DOI: 10.1186/s13195-023-01336-0
Abstrakt: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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