期刊
NEUROBIOLOGY OF AGING
卷 36, 期 6, 页码 2024-2033出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2015.03.004
关键词
Alzheimer's disease; Apolipoprotein E; Magnetic resonance imaging; Morris Water Maze; Neuropsychology; Memory; Hippocampus
资金
- Grant Agency of Charles University in Prague [624012, 546113, 1108214]
- European Regional Development Fund-Project FNUSA-ICRC [CZ.1.05/1.1.00/02.0123]
- project ICRC-ERA-HumanBridge [316345]
- European Social Fund
- State Budget of the Czech Republic
- European Social Fund within the project Young Talent Incubator II [CZ.1.07/2.3.00/20.0117]
- Ministry of Health, Czech Republic-conceptual development of research organization, University Hospital Motol, Prague, Czech Republic [00064203]
- Institutional Support of Laboratory Research [2/2012 (699002)]
- European Commission's Seventh Framework Programme (FP7) [283562]
- [AV0Z50110509]
- [RVO:67985823]
The very long (VL) poly-T variant at rs10524523 (523) of the TOMM40 gene may hasten the onset of late-onset Alzheimer's disease (LOAD) and induce more profound cognitive impairment compared with the short (S) poly-T variant. We examined the influence of TOMM40 523 polymorphism on spatial navigation and its brain structural correlates. Participants were apolipoprotein E (APOE) epsilon 3/epsilon 3 homozygotes with amnestic mild cognitive impairment (aMCI). The homozygotes were chosen because APOE epsilon 3/epsilon 3 variant is considered neutral with respect to LOAD risk. The participants were stratified according to poly-T length polymorphisms at 523 into homozygous for S (S/S; n = 16), homozygous for VL (VL/VL; n = 15) TOMM40 poly-T variant, and heterozygous (S/VL; n = 28) groups. Neuropsychological examination and testing in real-space human analog of the Morris Water Maze were administered. Both self-centered (egocentric) and world-centered (allocentric) spatial navigation was assessed. Brain magnetic resonance imaging scans were analyzed using FreeSurfer software. The S/S group, although similar to S/VL and VL/VL groups in demographic and neuropsychological profiles, performed better on allocentric navigation (p <= 0.004) and allocentric delayed recall (p <= 0.014), but not on egocentric navigation. Both S/VL and VL/VL groups had thinner right entorhinal cortex (p <= 0.043) than the S/S group, whereas only the VL/VL group had thinner left entorhinal cortex (p = 0.043) and left posterior cingulate cortex (p = 0.024) than the S/S group. In conclusion, TOMM40 523 VL variants are related to impairment in allocentric spatial navigation and reduced cortical thickness of specific brain regions among aMCI individuals with (LOAD neutral) APOE epsilon 3/epsilon 3 genotype. This may reflect a specific role of TOMM40 523 in the pathogenesis of LOAD. (C) 2015 Elsevier Inc. All rights reserved.
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