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.
| Original language | English |
|---|---|
| Pages (from-to) | 5792-5798 |
| Number of pages | 7 |
| Journal | Molecular Neurobiology |
| Volume | 56 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 15 2019 |
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Keywords
- Alzheimer’s disease
- Biomarker
- Exosomes
- Peripheral
- SNAP-25
- Synaptic proteins
ASJC Scopus subject areas
- Neuroscience (miscellaneous)
- Neurology
- Cellular and Molecular Neuroscience
Cite this
SNAP-25 in Serum Is Carried by Exosomes of Neuronal Origin and Is a Potential Biomarker of Alzheimer’s Disease. / Agliardi, Cristina; Guerini, Franca R.; Zanzottera, Milena; Bianchi, Anna; Nemni, Raffaello; Clerici, Mario.
In: Molecular Neurobiology, Vol. 56, No. 8, 15.08.2019, p. 5792-5798.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - SNAP-25 in Serum Is Carried by Exosomes of Neuronal Origin and Is a Potential Biomarker of Alzheimer’s Disease
AU - Agliardi, Cristina
AU - Guerini, Franca R.
AU - Zanzottera, Milena
AU - Bianchi, Anna
AU - Nemni, Raffaello
AU - Clerici, Mario
PY - 2019/8/15
Y1 - 2019/8/15
N2 - 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.
AB - 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.
KW - Alzheimer’s disease
KW - Biomarker
KW - Exosomes
KW - Peripheral
KW - SNAP-25
KW - Synaptic proteins
UR - http://www.scopus.com/inward/record.url?scp=85068774685&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068774685&partnerID=8YFLogxK
U2 - 10.1007/s12035-019-1501-x
DO - 10.1007/s12035-019-1501-x
M3 - Article
AN - SCOPUS:85068774685
VL - 56
SP - 5792
EP - 5798
JO - Molecular Neurobiology
JF - Molecular Neurobiology
SN - 0893-7648
IS - 8
ER -