SNARE Complex Polymorphisms Associate with Alterations of Visual Selective Attention in Alzheimer’s Disease

Article type: Research Article

Authors: Costa, Andrea Saul^{a; *} | Guerini, Franca Rosa^a | Arosio, Beatrice^{b; c} | Galimberti, Daniela^{d; e} | Zanzottera, Milena^a | Bianchi, Anna^a | Nemni, Raffaello^{a; e} | Clerici, Mario^{a; e}

Affiliations: [a] IRCCS Fondazione Don Carlo Gnocchi, Milan, Italy | [b] Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Geriatric Unit, Milan, Italy | [c] Department of Medical Sciences and Community Health, University of Milan, Milan, Italy | [d] Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Neurodegenerative Diseases Unit, Milan, Italy | [e] Department of Pathophysiology and Transplantation, University of Milano, Milano, Italy

Correspondence: [*] Correspondence to: Andrea Saul Costa, PhD, Don C. Gnocchi Foundation - ONLUS, IRCCS, P.zza Morandi, 3, 20100, Milan, Italy. Tel.: +39 0250330412; Fax: +39 02 50330414; E-mail: [email protected].

Abstract: The SNARE complex plays a crucial role in the synaptic exocytosis of neurotransmitters, a process involved in the Alzheimer’s disease (AD), the most common form of dementia. SNAP-25, STX1a, and VAMP2 are the core proteins of the SNARE complex, and changes in protein level are suggested to contribute to cognitive impairment and neuropsychiatric disorders. Single nucleotide polymorphisms (SNPs) in SNARE complex genes were shown to be associated with different diseases and different cognitive impairments. Chi-square analysis was used to compare case-control difference of ApoE4, SNAP-25 rs363039, rs363043, rs363950, STX1a rs4717806, rs2293489, and VAMP2 26bp Ins/Del genotype distribution in 192 AD, 187 mild cognitive impairment (MCI), and 200 healthy controls (HC). Results of genotype and allelic distribution of SNAP-25 rs363050 showed that AA genotype (AD versus HC: p = 1.5×10–4; MCI versus HC: p = 8.7×10–3) as well as A allele (AD versus HC: p = 6.0×10–4; MCI versus HC: p = 5.7×10–3) are significantly more frequent in AD and MCI compared to HC. Genotype distribution of STX1a rs4717806 and rs2293489 resulted significantly different in AD compared to HC (p = 0.032 and p = 0.047, respectively). Moreover, distribution of the STX1a rs4717806 allele in SNAP-25 rs363050 AA carriers was significantly different between MCI and HC (p = 0.018). Notably, in MCI, visual selective attention impairment was associated with the STX1a rs4717806 AA (pc = 0.027) genotype as well as the SNAP-25/STX1a rs363050/rs4717806 AA/A (pc = 0.022) combination. These data suggest that SNPs in SNARE complex genes may interfere and/or modulate the activity of the SNARE complex resulting in impairments of neurotransmission that involve attention brain areas.

Keywords: Alzheimer’s disease, cognitive impairment, gene polymorphisms, mild cognitive impairment, SNAP-25, SNARE, SNPs, STX1a, VAMP2

DOI: 10.3233/JAD-190147

Journal: Journal of Alzheimer's Disease, vol. 69, no. 1, pp. 179-188, 2019