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

Ferencz, Beata ; Laukka, Erika J. ; Lövdén, Martin LU ; Kalpouzos, Gregoria ; Keller, Lina ; Graff, Caroline ; Wahlund, Lars-Olof ; Fratiglioni, Laura and Backman, Lars (2013) In Frontiers in Human Neuroscience 7.
Abstract
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... (More)
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 6087 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 x 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 epsilon 4 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 epsilon 4 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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
APOE, TOMM40, episodic memory, hippocampus, cognitive aging
in
Frontiers in Human Neuroscience
volume
7
article number
198
publisher
Frontiers Media S. A.
external identifiers
  • wos:000319329800001
  • pmid:23734114
  • scopus:84982170242
ISSN
1662-5161
DOI
10.3389/fnhum.2013.00198
language
English
LU publication?
yes
id
b50dd88a-f6f0-48a5-bdef-9838cc95df3d (old id 3931627)
date added to LUP
2016-04-01 14:42:50
date last changed
2020-12-15 01:39:30
@article{b50dd88a-f6f0-48a5-bdef-9838cc95df3d,
  abstract     = {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 6087 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 x 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 &lt; 0.01, r(2) = 0.04). When further stratified for TOMM40, the observed association between HC volume and free recall in APOE epsilon 4 carriers was present in combination with TOMM40 rs11556505 any T (r = 0.28, p &lt; 0.01, R-2 = 0.08) and rs2075650 any G (r = 0.28, p &lt; 0.01, R-2 = 0.08) risk alleles. This pattern might reflect higher reliance on HC volume for adequate EM performance among APOE epsilon 4 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.},
  author       = {Ferencz, Beata and Laukka, Erika J. and Lövdén, Martin and Kalpouzos, Gregoria and Keller, Lina and Graff, Caroline and Wahlund, Lars-Olof and Fratiglioni, Laura and Backman, Lars},
  issn         = {1662-5161},
  language     = {eng},
  publisher    = {Frontiers Media S. A.},
  series       = {Frontiers in Human Neuroscience},
  title        = {The influence of APOE and TOMM40 polymorphisms on hippocampal volume and episodic memory in old age},
  url          = {http://dx.doi.org/10.3389/fnhum.2013.00198},
  doi          = {10.3389/fnhum.2013.00198},
  volume       = {7},
  year         = {2013},
}