VAMP-2 is a surrogate cerebrospinal fluid marker of Alzheimer-related cognitive impairment in adults with Down syndrome
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Le résumé fourni par la source
Abstract Background There is an urgent need for objective markers of Alzheimer’s disease (AD)-related cognitive impairment in people with Down syndrome (DS) to improve diagnosis, monitor disease progression, and assess response to disease-modifying therapies. Previously, GluA4 and neuronal pentraxin 2 (NPTX2) showed limited potential as cerebrospinal fluid (CSF) markers of cognitive impairment in adults with DS. Here, we compare the CSF profile of a panel of synaptic proteins (Calsyntenin-1, Neuroligin-2, Neurexin-2A, Neurexin-3A, Syntaxin-1B, Thy-1, VAMP-2) to that of NPTX2 and GluA4 in a large cohort of subjects with DS across the preclinical and clinical AD continuum and explore their correlation with cognitive impairment. Methods We quantified the synaptic panel proteins by selected reaction monitoring in CSF from 20 non-trisomic cognitively normal controls (mean age 44) and 80 adults with DS grouped according to clinical AD diagnosis (asymptomatic, prodromal AD or AD dementia). We used regression analyses to determine CSF changes across the AD continuum and explored correlations with age, global cognitive performance (CAMCOG), episodic memory (modified cued-recall test; mCRT) and CSF biomarkers, CSF Aβ42:40ratio, CSF Aβ1-42, CSF p-tau, and CSF NFL. P values were adjusted for multiple testing. Results In adults with DS, VAMP-2 was the only synaptic protein to correlate with episodic memory (delayed recalladj.p= .04) and age (adj.p= .0008) and was the best correlate of CSF Aβ42:40(adj.p= .0001), p-tau (adj.p <.0001), and NFL (adj.p <.0001). Compared to controls, mean VAMP-2 levels were lower in asymptomatic adults with DS only (adj.p= .02). CSF levels of Neurexin-3A, Thy-1, Neurexin-2A, Calysntenin-1, Neuroligin-2, GluA4, and Syntaxin-1B all strongly correlated with NPTX2 (p< .0001), which was the only synaptic protein to show reduced CSF levels in DS at all AD stages compared to controls (adj.p< .002). Conclusion These data show proof-of-concept for CSF VAMP-2 as a potential marker of synapse degeneration that correlates with CSF AD and axonal degeneration markers and cognitive performance.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- VAMP-2 is a surrogate cerebrospinal fluid marker of Alzheimer-related cognitive impairment in adults with Down syndrome
- Date Crossref
- 28/06/2021
- 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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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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Johns Hopkins University Solomon H. Snyder Department of Neuroscience pays non établi dans la noticeUniversité ou école supérieure
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Johns Hopkins Medicine pays non établi dans la noticeÉtablissement de santé
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Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) pays non établi dans la noticeInstitution
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Autonomous University of Barcelona Memory Unit and Biomedical Research Institute Sant Pau (IIB Sant Pau) pays non établi dans la noticeUniversité ou école supérieure
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Barcelona Down Medical Center pays non établi dans la noticeÉtablissement de santé
Universitat Autònoma de Barcelona, Hospital de Sant Pau et Biomedical Research Networking Center on Neurodegenerative Diseases, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.