The effect of TOMM40 on spatial navigation in amnestic mild cognitive impairment
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
25862420
DOI
10.1016/j.neurobiolaging.2015.03.004
PII: S0197-4580(15)00165-7
Knihovny.cz E-resources
- Keywords
- Alzheimer’s disease, Apolipoprotein E, Hippocampus, Magnetic resonance imaging, Memory, Morris Water Maze, Neuropsychology,
- MeSH
- Alzheimer Disease genetics pathology psychology MeSH
- Apolipoprotein E3 genetics MeSH
- Genotype MeSH
- Homozygote MeSH
- Cognitive Dysfunction genetics pathology psychology MeSH
- Middle Aged MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Membrane Transport Proteins genetics physiology MeSH
- Mitochondrial Precursor Protein Import Complex Proteins MeSH
- Cerebral Cortex pathology MeSH
- Neuropsychological Tests MeSH
- Polymorphism, Genetic * MeSH
- Spatial Navigation physiology MeSH
- Risk MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Apolipoprotein E3 MeSH
- Membrane Transport Proteins MeSH
- Mitochondrial Precursor Protein Import Complex Proteins MeSH
- TOMM40 protein, human MeSH Browser
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) ε3/ε3 homozygotes with amnestic mild cognitive impairment (aMCI). The homozygotes were chosen because APOE ε3/ε3 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 ε3/ε3 genotype. This may reflect a specific role of TOMM40 "523" in the pathogenesis of LOAD.
References provided by Crossref.org
Spatial navigation questionnaires as a supportive diagnostic tool in early Alzheimer's disease
Emotional prosody recognition is impaired in Alzheimer's disease
Spatial Navigation and Visuospatial Strategies in Typical and Atypical Aging
The Combined Effect of APOE and BDNF Val66Met Polymorphisms on Spatial Navigation in Older Adults
