> Details

Johnson, Sterling C.; La Rue, Asenath; Hermann, Bruce P.; Xu, Guofan; Koscik, Rebecca L.; Jonaitis, Erin M.; Bendlin, Barbara B.; Hogan, Kirk J.; Roses, Allen D.; Saunders, Ann M.; Lutz, Michael W.; Asthana, Sanjay; Green, Robert C.; Sager, Mark A.

The effect of TOMM40 poly‐T length on gray matter volume and cognition in middle‐aged persons with APOEɛ3/ɛ3 genotype

Reference
management

Bookmarks

Remove from
bookmarks

Share this on Whatsapp

Close

Bookmarks



You can manage bookmarks using lists, please log in to your user account for this.
  • Media type: E-Article
  • Title: The effect of TOMM40 poly‐T length on gray matter volume and cognition in middle‐aged persons with APOEɛ3/ɛ3 genotype
  • Contributor: Johnson, Sterling C.; La Rue, Asenath; Hermann, Bruce P.; Xu, Guofan; Koscik, Rebecca L.; Jonaitis, Erin M.; Bendlin, Barbara B.; Hogan, Kirk J.; Roses, Allen D.; Saunders, Ann M.; Lutz, Michael W.; Asthana, Sanjay; Green, Robert C.; Sager, Mark A.
  • imprint: Wiley, 2011
  • Published in: Alzheimer's & Dementia
  • Language: English
  • DOI: 10.1016/j.jalz.2010.11.012
  • ISSN: 1552-5279; 1552-5260
  • Keywords: Psychiatry and Mental health ; Cellular and Molecular Neuroscience ; Geriatrics and Gerontology ; Neurology (clinical) ; Developmental Neuroscience ; Health Policy ; Epidemiology
  • Origination:
  • Footnote:
  • Description: <jats:sec><jats:title>Objective</jats:title><jats:p>Apolipoprotein E (<jats:italic>APOE</jats:italic>) genotypes are associated with variable risk of developing late‐onset Alzheimer's disease (LOAD), with <jats:italic>APOE</jats:italic> epsilon 4 (<jats:italic>APOE</jats:italic> ɛ4) having higher risk. A variable poly‐T length polymorphism at rs10524523, within intron 6 of the translocase of the outer mitochondrial membrane (TOMM40) gene, has been shown to influence age of onset in LOAD, with very long (VL) poly‐T length associated with earlier disease onset, and short poly‐T length associated with later onset. In this study, we tested the hypothesis that brain and cognitive changes suggestive of presymptomatic LOAD may be associated with this <jats:italic>TOMM40</jats:italic> polymorphism.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Among healthy <jats:italic>APOE</jats:italic> ɛ3 homozygous adults (N = 117; mean age, 55 years), we compared those who were homozygous for VL/VL (n = 35) <jats:italic>TOMM40</jats:italic> poly‐T lengths (who were presumably at higher risk) with those homozygous for short (S/S; n = 38) poly‐T lengths, as well as those with heterozygous (S/VL; n = 44) poly‐T length polymorphisms, on measures of learning and memory and on structural brain imaging.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The VL/VL group showed lower performance than the S/S <jats:italic>TOMM40</jats:italic> group on primacy retrieval from a verbal list learning task, a finding which is also seen in early Alzheimer's disease. A dose‐dependent increase in the VL <jats:italic>TOMM40</jats:italic> polymorphism (from no VL alleles, to S/VL heterozygous, to VL/VL homozygous) was associated with decreasing gray matter volume in the ventral posterior cingulate and medial ventral precuneus, a region of the brain affected early in LOAD.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>These findings among APOE ɛ3/ɛ3 late middle‐aged adults suggest that a subgroup with VL <jats:italic>TOMM40</jats:italic> poly‐T lengths may be experiencing incipient LOAD‐related cognitive and brain changes.</jats:p></jats:sec>