• MeSH
• Alzheimerova nemoc patologie   MeSH
• hipokampus patologie   fyziologie   MeSH
• kognitivní dysfunkce patologie   MeSH
• lidé MeSH
• prostorová navigace * MeSH
• stárnutí * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• úvodníky MeSH

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.

• MeSH
• Alzheimerova nemoc genetika   patologie   psychologie   MeSH
• apolipoprotein E3 genetika   MeSH
• genotyp MeSH
• homozygot MeSH
• kognitivní dysfunkce genetika   patologie   psychologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• membránové transportní proteiny genetika   fyziologie   MeSH
• mozková kůra patologie   MeSH
• neuropsychologické testy MeSH
• polymorfismus genetický * MeSH
• prostorová navigace fyziologie   MeSH
• riziko MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH