NALP1/NLRP1 Genetic Variants are Associated With Alzheimer... : Alzheimer Disease & Associated Disorders (original) (raw)

Original Articles

Pontillo, Alessandra PhD*; Catamo, Eulalia BSc†; Arosio, Beatrice PhD‡; Mari, Daniela MD‡; Crovella, Sergio PhD§

*Institute for Maternal and Child Health IRCCS “Burlo Garofolo”

†Department of Medical Science, Surgery and Health, University of Trieste, Trieste

‡Geriatric Unit, Fondazione IRCCS “Cà Granda” Ospedale Maggiore Policlinico, Università degli Studi di Milano, Milano

§Institute for Maternal and Child Health IRCCS “Burlo Garofolo” and University of Trieste, Trieste, Italy

This study was supported by funds from IRCCS Burlo Garofolo (RC05/09). The study did not receive any funds from the following organizations: National Institutes of Health, Wellcome Trust, and Howard Hughes Medical Institute.

The authors declare no conflicts of interest.

Reprints: Alessandra Pontillo, PhD, Medical Genetic Service, Institute for Maternal and Child Health IRCCS “Burlo Garofolo,” Via dell’Istria, 65/1, 34137 Trieste, Italy (e-mail: [email protected]).

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Received March 11, 2011

Accepted July 23, 2011

Abstract

Alzheimer disease (AD) is a complex neurodegenerative disease. Genetic and molecular studies have confirmed that in the human brain, amyloid-β fibrils can induce, through the activation of NALP1 inflammosome, inflammatory and apoptotic responses involved in the pathogenesis of AD. Considering that AD pathogenesis is multifactorial, we hypothesized that NALP1/NLRP1 could be a susceptibility gene involved in the devolvement of the disease. The possible association between 9 selected polymorphisms in the NALP1/NLRP1 gene and AD was evaluated by comparing their frequency distribution in an Italian cohort of AD patients (AD, n=276) and in a group of Italian sex-matched and age-matched healthy controls without dementia (HC, n=266). Our study, evidences the association of 4 nonsynonymous polymorphisms in the NLRP1 gene (rs2137722, rs34733791, rs11657747, rs11651595) with AD. The major alleles of all 4 single nucleotide polymorphisms and the corresponding homozygote genotypes were more frequent in AD patients than in healthy controls, suggesting an association of these variants in the predisposition versus the development of the disease. These findings seem to support the previously reported role of NALP1 in neuronal damage, and provide evidence of an association between single nucleotide variations in the NLRP1 gene and AD.