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A Multi-Cohort Study of ApoE epsilon 4 and Amyloid-beta Effects on the Hippocampus in Alzheimer's Disease
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Number of Authors: 392017 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 56, no 3, p. 1159-1174Article in journal (Refereed) Published
Abstract [en]

The apolipoprotein E (APOE) gene has been consistently shown to modulate the risk of Alzheimer's disease (AD). Here, using an AD and normal aging dataset primarily consisting of three AD multi-center studies (n = 1,781), we compared the effect of APOE and amyloid-beta (A beta) on baseline hippocampal volumes in AD patients, mild cognitive impairment (MCI) subjects, and healthy controls. A large sample of healthy adolescents (n = 1,387) was also used to compare hippocampal volumes between APOE groups. Subjects had undergone a magnetic resonance imaging (MRI) scan and APOE genotyping. Hippocampal volumes were processed using FreeSurfer. In the AD and normal aging dataset, hippocampal comparisons were performed in each APOE group and in epsilon 4 carriers with positron emission tomography (PET) A beta who were dichotomized (A beta+/A beta-) using previous cut-offs. We found a linear reduction in hippocampal volumes with epsilon 4 carriers possessing the smallest volumes, epsilon 3 carriers possessing intermediate volumes, and epsilon 2 carriers possessing the largest volumes. Moreover, AD and MCI epsilon 4 carriers possessed the smallest hippocampal volumes and control epsilon 2 carriers possessed the largest hippocampal volumes. Subjects with both APOE epsilon 4 and A beta positivity had the lowest hippocampal volumes when compared to A beta-epsilon 4 carriers, suggesting a synergistic relationship between APOE epsilon 4 and A beta. However, we found no hippocampal volume differences between APOE groups in healthy 14-year-old adolescents. Our findings suggest that the strongest neuroanatomic effect of APOE epsilon 4 on the hippocampus is observed in AD and groups most at risk of developing the disease, whereas hippocampi of old and young healthy individuals remain unaffected.

Place, publisher, year, edition, pages
2017. Vol. 56, no 3, p. 1159-1174
Keywords [en]
Alzheimer's disease, amyloid, APOE epsilon 4, hippocampus, magnetic resonance imaging, mild cognitive impairment
National Category
Geriatrics
Identifiers
URN: urn:nbn:se:su:diva-166193DOI: 10.3233/JAD-161097ISI: 000395078900027PubMedID: 28157104OAI: oai:DiVA.org:su-166193DiVA, id: diva2:1297510
Available from: 2019-03-20 Created: 2019-03-20 Last updated: 2019-03-20Bibliographically approved

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Giampietro, VincentBarker, Gareth J.Frouin, VincentWilliams, Steven C. R.Simmons, Andrew
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Aging Research Center (ARC), (together with KI)
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