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SNAP-25 in Serum Is Carried by Exosomes of Neuronal Origin and Is a Potential Biomarker of Alzheimer’s Disease

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Abstract

A loss of synaptic density and connectivity is observed in multiple brain regions of Alzheimer’s disease (AD) patients, resulting in a reduced expression of synaptic proteins such as SNAP-25 (synaptosomal-associated-protein-25). SNAP-25 alterations thus could be an index of the degree of synaptic degeneration in the central nervous system (CNS). We isolated from serum of both AD patients and healthy controls (HC) a population of neuron-derived exosomes (NDEs) and measured the concentrations of SNAP-25 contained in such NDEs. The levels of SNAP-25 carried by NDEs were reduced in AD patients (mean 459.05 ng/ml, SD 146.35 ng/ml) compared to HC (mean 686.42 ng/ml, SD 204.08 ng/ml) (p < 0.001). As a further confirmation of these results, ROC (receiver operating characteristic) analyses indicated that the level of SNAP-25 carried by NDEs has the power to discriminate between AD and HC (AUC = 0.826, sensitivity = 87.5%, specificity = 70.6%, p < 0.0001, cut-off value 587.07 ng/ml). Notably, a correlation between the levels of SNAP-25 carried by NDEs and levels and cognitive status measured by MMSE score (r = 0.465, 95% CI 0.11 to 0.714, p = 0.01) was detected. This is the first report of SNAP-25 measurement in serum. These data suggest that NDE-carried SNAP-25 could be an effective and accessible biomarker that reflects synapses integrity in the brain.

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Funding

This work was supported by Italian Ministry of Health (Ricerca Corrente 2018).

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Authors and Affiliations

  1. Laboratory of Molecular Medicine and Biotechnology, IRCCS Fondazione Don Carlo Gnocchi, Via Capecelatro 66, 20148, Milan, Italy

    Cristina Agliardi, Franca R. Guerini, Milena Zanzottera, Anna Bianchi, Raffaello Nemni & Mario Clerici

  2. Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

    Raffaello Nemni & Mario Clerici

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  1. Cristina Agliardi
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  2. Franca R. Guerini
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  3. Milena Zanzottera
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Correspondence to Cristina Agliardi.

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The study conformed to the ethical principles of the Helsinki Declaration. The Ethical Committee of the Don C. Gnocchi Foundation IRCCS approved the study (Prot. N°10/2018/CE_FdG/SA); all the participants when possible, or patients’ legal guardians when it was not, gave informed consent.

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Agliardi, C., Guerini, F.R., Zanzottera, M. et al. SNAP-25 in Serum Is Carried by Exosomes of Neuronal Origin and Is a Potential Biomarker of Alzheimer’s Disease. Mol Neurobiol 56, 5792–5798 (2019). https://doi.org/10.1007/s12035-019-1501-x

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