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.

SNAP-25 in Serum Is Carried by Exosomes of Neuronal Origin and Is a Potential Biomarker of Alzheimer's Disease / C. Agliardi, F.R. Guerini, M. Zanzottera, A. Bianchi, R. Nemni, M. Clerici. - In: MOLECULAR NEUROBIOLOGY. - ISSN 0893-7648. - (2019 Jan 24). [Epub ahead of print] [10.1007/s12035-019-1501-x]

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

C. Agliardi
Primo
;
F.R. Guerini
Secondo
;
R. Nemni
Penultimo
;
M. Clerici
Ultimo
2019-01-24

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.
Alzheimer’s disease; Biomarker; Exosomes; Peripheral; SNAP-25; Synaptic proteins
Settore MED/04 - Patologia Generale
Settore MED/26 - Neurologia
Settore MED/03 - Genetica Medica
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/617020
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