Possible association between SNAP-25 single nucleotide polymorphisms and alterations of categorical fluency and functional MRI parameters in Alzheimer's disease

Franca Rosa Guerini, Cristina Agliardi, Manuela Sironi, Beatrice Arosio, Elena Calabrese, Milena Zanzottera, Elisabetta Bolognesi, Cristian Ricci, Andrea Saul Costa, Daniela Galimberti, Ludovica Griffanti, Anna Bianchi, Federica Savazzi, Daniela Mari, Elio Scarpini, Francesca Baglio, Raffaello Nemni, Mario Clerici

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1015-1028
Number of pages14
JournalJournal of Alzheimer's Disease
Volume42
Issue number3
DOIs
Publication statusPublished - 2014

Keywords

  • Alzheimer's disease
  • categorical fluency
  • cognitive impairment
  • functional MRI
  • genetic polymorphisms
  • SNAP-25

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology
  • Medicine(all)

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