title: TOMM40 intron 6 poly-T length, age at onset, and neuropathology of AD in individuals with APOE ε3/ε3.
abstract: BACKGROUND
  This study investigates the association between TOMM40 poly-T length, age at onset, and neuropathology in individuals with Alzheimer's disease (AD) with the apolipoprotein E (APOE) ε3/ε3 allele.
  
  
  METHODS
  Thirty-two presenilin 1 (PSEN1) mutation carriers with AD, 27 presenilin 2 (PSEN2) mutation carriers with AD, 59 participants with late-onset AD (LOAD), and 168 autopsied subjects from a community-based cohort were genotyped for TOMM40 intron 6 poly-T (rs10524523) length using short tandem repeat assays.
  
  
  RESULTS
  Among AD individuals with PSEN2 mutations, the presence of a long poly-T was associated with an earlier age at onset, whereas there were no such associations for subjects with PSEN1 mutations or LOAD. In community-based participants, the presence of a long poly-T was associated with increased neuritic tangles and a greater likelihood of pathologically diagnosed AD.
  
  
  CONCLUSIONS
  TOMM40 intron 6 poly-T length may explain some of the variation in age at onset in PSEN2 familial AD and may be associated with AD neuropathology in persons with APOE ε3/ε3.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. gli@u.washington.edu
authors.forename: Ge
authors.initials: G
authors.lastname: Li
authors.forename: Lynn M
authors.initials: LM
authors.lastname: Bekris
authors.forename: Lesley
authors.initials: L
authors.lastname: Leong
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Steinbart
authors.forename: Jane B
authors.initials: JB
authors.lastname: Shofer
authors.forename: Paul K
authors.initials: PK
authors.lastname: Crane
authors.forename: Eric B
authors.initials: EB
authors.lastname: Larson
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Bird
authors.forename: Chang-En
authors.initials: CE
authors.lastname: Yu
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053318:Apolipoprotein E3 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007438:Introns; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009154:Mutation; D011071:Poly T / Q000235:genetics; D053764:Presenilin-1 / Q000235:genetics; D053766:Presenilin-2 / Q000235:genetics
chemical_list: D053318:Apolipoprotein E3; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C508853:PSEN1 protein, human; C508861:PSEN2 protein, human; D053764:Presenilin-1; D053766:Presenilin-2; C400783:TOMM40 protein, human; D011071:Poly T