title: Possible association between SNAP-25 single nucleotide polymorphisms and alterations of categorical fluency and functional MRI parameters in Alzheimer's disease.
abstract: Synaptosomal-associated protein of 25 kDa (SNAP-25) is an age-regulated vesicular SNARE protein involved in the exocytosis of neurotransmitters from synapses, a process that is altered in Alzheimer's disease (AD). Changes in SNAP-25 levels are suggested to contribute to age-related decline of cognitive function, and single nucleotide polymorphisms (SNPs) in the SNAP-25 gene are present in neuropsychiatric conditions and play a role in determining IQ phenotypes. To verify a possible role of SNAP-25 in AD, we analyzed five gene polymorphisms in patients with AD (n = 607), replicating the study in subjects with amnestic mild cognitive impairment (aMCI) (n = 148) and in two groups of age-matched healthy controls (HC1: n = 615 and HC2: n = 310). Results showed that the intronic rs363050 (A) and rs363043 (T) alleles, as well as the rs363050/rs363043 A-T haplotype are significantly more frequent in AD and aMCI and are associated with pathological scores of categorical fluency in AD. Notably, functional MRI analyses indicated that SNAP-25 genotypes correlate with a significantly decreased brain activity in the cingulate cortex and in the frontal (middle and superior gyri) and the temporo-parietal (angular gyrus) area. SNAP-25 polymorphisms may be associated with AD and correlate with alterations in categorical fluency and a reduced localized brain activity. SNAP-25 polymorphisms could be used as surrogate markers for the diagnosis of AD and of cognitive deficit; these SNPs might also have a possible predictive role in the natural history of AD.
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy.
authors.forename: Franca Rosa
authors.initials: FR
authors.lastname: Guerini
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Agliardi
authors.affiliation: Scientific Institute IRCCS E. Medea, Bosisio Parini (LC), Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Sironi
authors.affiliation: Geriatric Unit, Department of Clinical Sciences and Community, University of Milano, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arosio
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Calabrese
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Zanzottera
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bolognesi
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy Department of Epidemiology and Preventative Medicine, University of Regensburg, Regensburg, Germany.
authors.forename: Cristian
authors.initials: C
authors.lastname: Ricci
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy.
authors.forename: Andrea Saul
authors.initials: AS
authors.lastname: Costa
authors.affiliation: Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milano, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Galimberti
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy Bioengineering Department, Politecnico of Milano, Milano, Italy.
authors.forename: Ludovica
authors.initials: L
authors.lastname: Griffanti
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Bianchi
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Savazzi
authors.affiliation: Geriatric Unit, Department of Clinical Sciences and Community, University of Milano, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mari
authors.affiliation: Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milano, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milano, Italy.
authors.forename: Elio
authors.initials: E
authors.lastname: Scarpini
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Baglio
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy Department of Pathophysiology and Transplantation University of Milano, Milano, Italy.
authors.forename: Raffaello
authors.initials: R
authors.lastname: Nemni
authors.affiliation: Don C. Gnocchi Foundation IRCCS, Milano, Italy Department of Pathophysiology and Transplantation University of Milano, Milano, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000098:blood supply*; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000209:etiology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011594:Psychometrics; D018709:Statistics, Nonparametric; D050825:Synaptosomal-Associated Protein 25 / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; C494208:SNAP25 protein, human; D050825:Synaptosomal-Associated Protein 25; D010100:Oxygen
keywords: Alzheimer's disease; SNAP-25; categorical fluency; cognitive impairment; functional MRI; genetic polymorphisms