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J Alzheimers Dis. 2014;42(3):1015-28. doi: 10.3233/JAD-140057.

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

Author information

1
Don C. Gnocchi Foundation IRCCS, Milano, Italy.
2
Scientific Institute IRCCS E. Medea, Bosisio Parini (LC), Italy.
3
Geriatric Unit, Department of Clinical Sciences and Community, University of Milano, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milano, Italy.
4
Don C. Gnocchi Foundation IRCCS, Milano, Italy Department of Epidemiology and Preventative Medicine, University of Regensburg, Regensburg, Germany.
5
Dino Ferrari Center, Department of Pathophysiology and Transplantation, University of Milano, Fondazione Ca' Granda, IRCCS Ospedale Maggiore Policlinico, Milano, Italy.
6
Don C. Gnocchi Foundation IRCCS, Milano, Italy Bioengineering Department, Politecnico of Milano, Milano, Italy.
7
Don C. Gnocchi Foundation IRCCS, Milano, Italy Department of Pathophysiology and Transplantation University of Milano, Milano, Italy.

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.

KEYWORDS:

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

PMID:
25024311
DOI:
10.3233/JAD-140057
[Indexed for MEDLINE]

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