Cargando…

The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age

Mitochondrial dysfunction is implicated in neurodegenerative disorders, such as Alzheimer's disease (AD). Translocase of outer mitochondrial membrane 40 (TOMM40) may be influential in this regard by influencing mitochondrial neurotoxicity. Little is known about the influence of the TOMM40 gene...

Descripción completa

Detalles Bibliográficos
Autores principales: Ferencz, Beata, Laukka, Erika J., Lövdén, Martin, Kalpouzos, Grégoria, Keller, Lina, Graff, Caroline, Wahlund, Lars-Olof, Fratiglioni, Laura, Bäckman, Lars
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660657/
https://www.ncbi.nlm.nih.gov/pubmed/23734114
http://dx.doi.org/10.3389/fnhum.2013.00198
_version_ 1782270591409061888
author Ferencz, Beata
Laukka, Erika J.
Lövdén, Martin
Kalpouzos, Grégoria
Keller, Lina
Graff, Caroline
Wahlund, Lars-Olof
Fratiglioni, Laura
Bäckman, Lars
author_facet Ferencz, Beata
Laukka, Erika J.
Lövdén, Martin
Kalpouzos, Grégoria
Keller, Lina
Graff, Caroline
Wahlund, Lars-Olof
Fratiglioni, Laura
Bäckman, Lars
author_sort Ferencz, Beata
collection PubMed
description Mitochondrial dysfunction is implicated in neurodegenerative disorders, such as Alzheimer's disease (AD). Translocase of outer mitochondrial membrane 40 (TOMM40) may be influential in this regard by influencing mitochondrial neurotoxicity. Little is known about the influence of the TOMM40 gene on hippocampal (HC) volume and episodic memory (EM), particularly in healthy older adults. Thus, we sought to discern the influence of TOMM40 single nucleotide polymorphisms (SNPs), which have previously been associated with medial temporal lobe integrity (rs11556505 and rs2075650), on HC volume and EM. The study sample consisted of individuals from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who were free of dementia and known neurological disorders, and 60–87 years of age (n = 424). EM was measured by using a 16-item word list with a 2-min free recall period and delineation of the HC was performed manually. The influence of Apolipoprotein E (APOE) and TOMM40 was assessed by 2 × 2 ANOVAs and partial correlations. There was no effect of APOE and TOMM40 on EM performance and HC volume. However, partial correlations revealed that HC volume was positively associated with free recall performance (r = 0.21, p < 0.01, r(2) = 0.04). When further stratified for TOMM40, the observed association between HC volume and free recall in APOE ε4 carriers was present in combination with TOMM40 rs11556505 any T (r = 0.28, p < 0.01, R(2) = 0.08) and rs2075650 any G (r = 0.28, p < 0.01, R(2) = 0.08) “risk” alleles. This pattern might reflect higher reliance on HC volume for adequate EM performance among APOE ε4 carriers with additional TOMM40 “risk” alleles suggesting that the TOMM40 gene cannot merely be considered a marker of APOE genotype. Nevertheless, neither APOE nor TOMM40 influenced HC volume or EM in this population-based sample of cognitively intact individuals over the age of 60.
format Online
Article
Text
id pubmed-3660657
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-36606572013-06-03 The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age Ferencz, Beata Laukka, Erika J. Lövdén, Martin Kalpouzos, Grégoria Keller, Lina Graff, Caroline Wahlund, Lars-Olof Fratiglioni, Laura Bäckman, Lars Front Hum Neurosci Neuroscience Mitochondrial dysfunction is implicated in neurodegenerative disorders, such as Alzheimer's disease (AD). Translocase of outer mitochondrial membrane 40 (TOMM40) may be influential in this regard by influencing mitochondrial neurotoxicity. Little is known about the influence of the TOMM40 gene on hippocampal (HC) volume and episodic memory (EM), particularly in healthy older adults. Thus, we sought to discern the influence of TOMM40 single nucleotide polymorphisms (SNPs), which have previously been associated with medial temporal lobe integrity (rs11556505 and rs2075650), on HC volume and EM. The study sample consisted of individuals from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) who were free of dementia and known neurological disorders, and 60–87 years of age (n = 424). EM was measured by using a 16-item word list with a 2-min free recall period and delineation of the HC was performed manually. The influence of Apolipoprotein E (APOE) and TOMM40 was assessed by 2 × 2 ANOVAs and partial correlations. There was no effect of APOE and TOMM40 on EM performance and HC volume. However, partial correlations revealed that HC volume was positively associated with free recall performance (r = 0.21, p < 0.01, r(2) = 0.04). When further stratified for TOMM40, the observed association between HC volume and free recall in APOE ε4 carriers was present in combination with TOMM40 rs11556505 any T (r = 0.28, p < 0.01, R(2) = 0.08) and rs2075650 any G (r = 0.28, p < 0.01, R(2) = 0.08) “risk” alleles. This pattern might reflect higher reliance on HC volume for adequate EM performance among APOE ε4 carriers with additional TOMM40 “risk” alleles suggesting that the TOMM40 gene cannot merely be considered a marker of APOE genotype. Nevertheless, neither APOE nor TOMM40 influenced HC volume or EM in this population-based sample of cognitively intact individuals over the age of 60. Frontiers Media S.A. 2013-05-22 /pmc/articles/PMC3660657/ /pubmed/23734114 http://dx.doi.org/10.3389/fnhum.2013.00198 Text en Copyright © 2013 Ferencz, Laukka, Lövdén, Kalpouzos, Keller, Graff, Wahlund, Fratiglioni and Bäckman. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc.
spellingShingle Neuroscience
Ferencz, Beata
Laukka, Erika J.
Lövdén, Martin
Kalpouzos, Grégoria
Keller, Lina
Graff, Caroline
Wahlund, Lars-Olof
Fratiglioni, Laura
Bäckman, Lars
The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age
title The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age
title_full The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age
title_fullStr The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age
title_full_unstemmed The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age
title_short The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age
title_sort influence of apoe and tomm40 polymorphisms on hippocampal volume and episodic memory in old age
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660657/
https://www.ncbi.nlm.nih.gov/pubmed/23734114
http://dx.doi.org/10.3389/fnhum.2013.00198
work_keys_str_mv AT ferenczbeata theinfluenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT laukkaerikaj theinfluenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT lovdenmartin theinfluenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT kalpouzosgregoria theinfluenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT kellerlina theinfluenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT graffcaroline theinfluenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT wahlundlarsolof theinfluenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT fratiglionilaura theinfluenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT backmanlars theinfluenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT ferenczbeata influenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT laukkaerikaj influenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT lovdenmartin influenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT kalpouzosgregoria influenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT kellerlina influenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT graffcaroline influenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT wahlundlarsolof influenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT fratiglionilaura influenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage
AT backmanlars influenceofapoeandtomm40polymorphismsonhippocampalvolumeandepisodicmemoryinoldage