title: NALP1/NLRP1 genetic variants are associated with Alzheimer disease.
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.
authors.affiliation: Institute for Maternal and Child Health IRCCS Burlo Garofolo, University of Trieste, Trieste, Italy. pontillo@burlo.trieste.it
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pontillo
authors.forename: Eulalia
authors.initials: E
authors.lastname: Catamo
authors.forename: Beatrice
authors.initials: B
authors.lastname: Arosio
authors.forename: Daniela
authors.initials: D
authors.lastname: Mari
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D000070576:NLR Proteins; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000070576:NLR Proteins; C427903:NLRP1 protein, human