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P2‐174: Impulsivity in Alzheimer’s Disease as Detected by D‐CPT
Author(s) -
Topcular Baris,
Akin Ozge,
Tuncer Ozlem Gungor,
Matur Zeliha,
Altunrende Burcu,
Altindag Ebru,
Demir Gulsen Akman
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1341
Subject(s) - impulsivity , neuropsychology , executive dysfunction , dementia , medicine , disease , executive functions , correlation , stage (stratigraphy) , psychiatry , psychology , pediatrics , cognition , paleontology , geometry , mathematics , biology
Background: Genetic studies identified an association between Alzheimer’s disease (AD) and common polymorphisms in the MS4A and TREM loci, each containing cluster of homologous genes. Methods:We searched for rare coding variants in 15 genes mapped to these loci by next generation sequencing of a North American dataset (210 cases and 233 controls). Results:Analysis of the MS4A gene-cluster revealed loss-of-function variants in 6 controls and 3 cases. Investigation of the TREM gene-cluster detected known AD associated TREM2 substitutions (p.R47H, p.D87N and p.H157Y) affecting both TREM2 isoforms (NM_018965 and NM_001271821). We also identified two cases with novel TREM2 variants (p.L205P and p.G219C), which mapped only to the isoform NM_001271821. A p.S248R substitution in the homologous TREML2 gene was detected in 5 controls and 1 case suggesting a protective effect (pooled p-value 1⁄4 0.033). Conclusions:Our study advocates for the importance of mutation analysis of controls, particularly for GWAS loci containing SNPs with a minor allele frequency higher in controls versus cases (e.g. MS4A locus), to search for functional variants with a protective effect.