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Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults

Alzheimer’s disease (AD) risk genes alter brain structure and function decades before disease onset. Apolipoprotein E (APOE) is the strongest known genetic risk factor for AD, and a related gene, apolipoprotein J (APOJ), also affects disease risk. However, the extent to which these genes affect brai...

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Autores principales: DiBattista, Amanda Marie, Stevens, Benson W., Rebeck, G. William, Green, Adam E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186290/
https://www.ncbi.nlm.nih.gov/pubmed/25339884
http://dx.doi.org/10.3389/fnhum.2014.00779
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author DiBattista, Amanda Marie
Stevens, Benson W.
Rebeck, G. William
Green, Adam E.
author_facet DiBattista, Amanda Marie
Stevens, Benson W.
Rebeck, G. William
Green, Adam E.
author_sort DiBattista, Amanda Marie
collection PubMed
description Alzheimer’s disease (AD) risk genes alter brain structure and function decades before disease onset. Apolipoprotein E (APOE) is the strongest known genetic risk factor for AD, and a related gene, apolipoprotein J (APOJ), also affects disease risk. However, the extent to which these genes affect brain structure in young adults remains unclear. Here, we report that AD risk alleles of these two genes, APOE-ε4 and APOJ-C, cumulatively alter brain volume in young adults. Using voxel-based morphometry (VBM) in 57 individuals, we examined the entorhinal cortex, one of the earliest brain regions affected in AD pathogenesis. Apolipoprotein E-ε4 carriers exhibited higher right entorhinal cortex volume compared to non-carriers. Interestingly, APOJ-C risk genotype was associated with higher bilateral entorhinal cortex volume in non-APOE-ε4 carriers. To determine the combined disease risk of APOE and APOJ status per subject, we used cumulative odds ratios as regressors for volumetric measurements. Higher disease risk corresponded to greater right entorhinal cortex volume. These results suggest that, years before disease onset, two key AD genetic risk factors may exert influence on the structure of a brain region where AD pathogenesis takes root.
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spelling pubmed-41862902014-10-22 Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults DiBattista, Amanda Marie Stevens, Benson W. Rebeck, G. William Green, Adam E. Front Hum Neurosci Neuroscience Alzheimer’s disease (AD) risk genes alter brain structure and function decades before disease onset. Apolipoprotein E (APOE) is the strongest known genetic risk factor for AD, and a related gene, apolipoprotein J (APOJ), also affects disease risk. However, the extent to which these genes affect brain structure in young adults remains unclear. Here, we report that AD risk alleles of these two genes, APOE-ε4 and APOJ-C, cumulatively alter brain volume in young adults. Using voxel-based morphometry (VBM) in 57 individuals, we examined the entorhinal cortex, one of the earliest brain regions affected in AD pathogenesis. Apolipoprotein E-ε4 carriers exhibited higher right entorhinal cortex volume compared to non-carriers. Interestingly, APOJ-C risk genotype was associated with higher bilateral entorhinal cortex volume in non-APOE-ε4 carriers. To determine the combined disease risk of APOE and APOJ status per subject, we used cumulative odds ratios as regressors for volumetric measurements. Higher disease risk corresponded to greater right entorhinal cortex volume. These results suggest that, years before disease onset, two key AD genetic risk factors may exert influence on the structure of a brain region where AD pathogenesis takes root. Frontiers Media S.A. 2014-10-06 /pmc/articles/PMC4186290/ /pubmed/25339884 http://dx.doi.org/10.3389/fnhum.2014.00779 Text en Copyright © 2014 DiBattista, Stevens, Rebeck and Green. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
DiBattista, Amanda Marie
Stevens, Benson W.
Rebeck, G. William
Green, Adam E.
Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults
title Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults
title_full Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults
title_fullStr Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults
title_full_unstemmed Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults
title_short Two Alzheimer’s disease risk genes increase entorhinal cortex volume in young adults
title_sort two alzheimer’s disease risk genes increase entorhinal cortex volume in young adults
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4186290/
https://www.ncbi.nlm.nih.gov/pubmed/25339884
http://dx.doi.org/10.3389/fnhum.2014.00779
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