title: The effect of TOMM40 on spatial navigation in amnestic mild cognitive impairment.
abstract: 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.
authors: Memory Clinic, Department of Neurology, Charles University in Prague, Second Faculty of Medicine and Motol University Hospital, Prague, The Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Brno, The Czech Republic. Electronic address: JanLaczo@seznam.cz.
authors: Jan
authors: J
authors: Laczó
authors: International Clinical Research Center, St. Anne's University Hospital Brno, Brno, The Czech Republic; School of Aging Studies, University of South Florida, Tampa, FL, USA.
authors: Ross
authors: R
authors: Andel
authors: Memory Clinic, Department of Neurology, Charles University in Prague, Second Faculty of Medicine and Motol University Hospital, Prague, The Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Brno, The Czech Republic.
authors: Martin
authors: M
authors: Vyhnalek
authors: Department of Clinical Biochemistry, Hematology and Immunology, Homolka Hospital, Prague, The Czech Republic.
authors: Vaclav
authors: V
authors: Matoska
authors: Department of Clinical Biochemistry, Hematology and Immunology, Homolka Hospital, Prague, The Czech Republic.
authors: Vojtech
authors: V
authors: Kaplan
authors: Memory Clinic, Department of Neurology, Charles University in Prague, Second Faculty of Medicine and Motol University Hospital, Prague, The Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Brno, The Czech Republic.
authors: Zuzana
authors: Z
authors: Nedelska
authors: Memory Clinic, Department of Neurology, Charles University in Prague, Second Faculty of Medicine and Motol University Hospital, Prague, The Czech Republic.
authors: Ondrej
authors: O
authors: Lerch
authors: Memory Clinic, Department of Neurology, Charles University in Prague, Second Faculty of Medicine and Motol University Hospital, Prague, The Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Brno, The Czech Republic.
authors: Ivana
authors: I
authors: Gazova
authors: School of Psychology, Georgia Institute of Technology, Atlanta, GA, USA.
authors: Scott D
authors: SD
authors: Moffat
authors: Memory Clinic, Department of Neurology, Charles University in Prague, Second Faculty of Medicine and Motol University Hospital, Prague, The Czech Republic; International Clinical Research Center, St. Anne's University Hospital Brno, Brno, The Czech Republic.
authors: Jakub
authors: J
authors: Hort
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology / Q000523:psychology; D053318:Apolipoprotein E3 / Q000235:genetics; D002540:Cerebral Cortex / Q000473:pathology; D060825:Cognitive Dysfunction / Q000235:genetics* / Q000473:pathology / Q000523:psychology*; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000502:physiology*; D008875:Middle Aged; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D012306:Risk; D065854:Spatial Navigation / Q000502:physiology*
chemical_list: D053318:Apolipoprotein E3; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human
keywords: Alzheimer’s disease; Apolipoprotein E; Hippocampus; Magnetic resonance imaging; Memory; Morris Water Maze; Neuropsychology