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Serum miRNAs Expression and SNAP-25 Genotype in Alzheimer's Disease.

ABSTRACT: MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by binding their 3' untranslated region (3'UTR) region; these molecules play a fundamental role in several pathologies, including Alzheimer's disease (AD). Synaptosomal-associated protein of 25 kDa (SNAP-25) is a vesicular protein of soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) involved in neural plasticity and in the exocytosis of neurotransmitters, processes that are altered in AD. Recent results showed that a reduction of SNAP-25 is associated with dementia, and that the rs363050 SNAP-25 polymorphism correlates with cognitive decline and brain atrophy, as well as with the outcome of multistructured rehabilitation in AD patients. We verified the presence of possible correlations between the serum concentration of miRNAs that bind the SNAP-25 3'UTR region and AD. Six different microRNAs (miR-181a-5p, miR-361-3p, miR-23a-3p, miR-15b-3p, 130a-3p and miR-27b-3p) that bind the SNAP-25 3'UTR region were measured by qPCR in serum of AD patients (n = 22), mild cognitive impairment (MCI) subjects (n = 22) and age- and sex-matched controls (n = 22); analysis of results was done stratified for the rs363050 SNAP-25 genotype. Results showed that miR-27b-3p, miR-23a-3p and miR181a-5p serum concentration was significantly reduced in rs363050 SNAP-25 GG homozygous AD patients. Notably, concentration of these miRNAs was comparable in rs363050 AA homozygous AD patients, MCI and healthy controls (HCs). Data herein suggest that miRNAs that bind the SNAP-25 3'UTR region interact with SNAP-25 polymorphisms to influence the neural plasticity typical of AD brains, possibly as a consequence of modulatory activity on SNAP-25 mRNA and/or protein.

SUBMITTER: Agostini S

PROVIDER: S-EPMC6421304 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Serum miRNAs Expression and SNAP-25 Genotype in Alzheimer's Disease.

Agostini Simone S Mancuso Roberta R Liuzzo Gaia G Bolognesi Elisabetta E Costa Andrea Saul AS Bianchi Anna A Clerici Mario M

Frontiers in aging neuroscience 20190311

MicroRNAs (miRNAs) are small non-coding RNAs that control gene expression by binding their 3' untranslated region (3'UTR) region; these molecules play a fundamental role in several pathologies, including Alzheimer's disease (AD). Synaptosomal-associated protein of 25 kDa (SNAP-25) is a vesicular protein of soluble <i>N</i>-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) involved in neural plasticity and in the exocytosis of neurotransmitters, processes that are altered in AD. ...[more]

PMID: 30914946

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Project description:BackgroundThere is currently a lack of reliable and easily accessible biomarkers predicting cognitive decline in Alzheimer's disease (AD). Synaptic dysfunction and loss occur early in AD and synaptic loss measured in the brain tissue and by PET are closely linked to cognitive decline, rendering synaptic proteins a promising target for biomarker development.MethodsWe used novel Simoa assays to measure cerebrospinal fluid (CSF) levels of two synaptic biomarker candidates, postsynaptic density protein 95 (PSD-95/DLG4), and the presynaptically localized synaptosomal-associated protein 25 (SNAP-25), as well as neurogranin (Ng), an established postsynaptic biomarker. CSF samples from two well-characterized cohorts (n=178 and n=156) were selected from banked samples obtained from diagnostic lumbar punctures containing subjects with amyloid-ß (Aß) positive AD, subjects with non-AD neurodegenerative diseases, subjects with other neurological conditions, and healthy controls (HC).ResultsAll subjects had detectable CSF levels of PSD-95, SNAP-25, and Ng. CSF levels of PSD-95, SNAP-25, and Ng were all correlated, with the strongest correlation between the presynaptic SNAP-25 and the postsynaptic neurogranin. AD subjects had on average higher concentrations of all three synaptic markers compared to those with non-AD neurodegenerative diseases, other neurological disorders, and HCs. Increased CSF levels of PSD-95, SNAP-25, and Ng were, however, not specific for AD and were present in sporadic cases with inflammatory or vascular disorders as well. High CSF levels of PSD-95 were also observed in a few subjects with other neurodegenerative disorders.ConclusionThe data establishes PSD-95 as a promising CSF marker for neurodegenerative disease synaptic pathology, while SNAP-25 and Ng appear to be somewhat more specific for AD. Together, these synaptic markers hold promise to identify early AD pathology, to correlate with cognitive decline, and to monitor responses to disease-modifying drugs reducing synaptic degeneration.

Dataset Information

Serum miRNAs Expression and SNAP-25 Genotype in Alzheimer's Disease.

Publications

Serum miRNAs Expression and SNAP-25 Genotype in Alzheimer's Disease.

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