title: Biochemical studies of poly-T variants in the Alzheimer's disease associated TOMM40 gene.
abstract: The apolipoprotein E (APOE) gene remains the most strongly established risk factor for late onset Alzheimer's disease (LOAD). Recently the gene, TOMM40, which is in linkage disequilibrium with APOE, was identified to be associated with LOAD in genome-wide association studies. One of the identified polymorphisms in TOMM40 is rs10524523, which is located in intron 6 and composed of thymidine repeats varying between 14 to 36 base-pairs in length. Reported results are contradictory in regard to the very long poly-T variant that has been associated with both increased and decreased risk of LOAD. Our study aimed to elucidate the functional implication of rs10524523 in an in vitro model of human fibroblast cells obtained from cognitively healthy APOE ε3/ε4 carriers harboring very long or short poly-T variants coupled to their APOE ε3 allele. We have studied (i) expression levels of TOM40 protein and mRNA, (ii) TOM40 mRNA splicing, and (iii) mitochondrial function and morphology; and we have found no significant differences in regards to very long or short poly-T variant.
authors.affiliation: KI-Alzheimer's Disease Research Center, Karolinska Institutet, Department of Neurobiology, Care Sciences and Society (NVS), Stockholm, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Hedskog
authors.forename: Jesper
authors.initials: J
authors.lastname: Brohede
authors.forename: Birgitta
authors.initials: B
authors.lastname: Wiehager
authors.forename: Catarina Moreira
authors.initials: CM
authors.lastname: Pinho
authors.forename: Priya
authors.initials: P
authors.lastname: Revathikumar
authors.forename: Lena
authors.initials: L
authors.lastname: Lilius
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Glaser
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
authors.forename: Helena
authors.initials: H
authors.lastname: Karlström
authors.forename: Maria
authors.initials: M
authors.lastname: Ankarcrona
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000235:genetics*; D002478:Cells, Cultured; D016208:Databases, Factual; D005260:Female; D005347:Fibroblasts / Q000737:chemistry / Q000502:physiology; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011071:Poly T / Q000235:genetics*
chemical_list: D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human; D011071:Poly T