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Apolipoprotein E homozygous ε4 allele status: effects on cortical structure and white matter integrity in a young to mid-age sample

Apolipoprotein E (APOE) genotype is the strongest single gene predictor of Alzheimer's disease (AD) and has been frequently associated with AD-related brain structural alterations before the onset of dementia. While previous research has primarily focused on hippocampal morphometry in relation...

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Main Authors: Goltermann, Janik (Author) , Repple, Jonathan (Author) , Redlich, Ronny (Author) , Dohm, Katharina (Author) , Flint, Claas (Author) , Grotegerd, Dominik (Author) , Waltemate, Lena (Author) , Lemke, Hannah (Author) , Fingas, Stella Mercedes (Author) , Meinert, Susanne (Author) , Enneking, Verena (Author) , Hahn, Tim (Author) , Bauer, Jochen (Author) , Schmitt, Simon (Author) , Meller, Tina (Author) , Stein, Frederike (Author) , Brosch, Katharina (Author) , Steinsträter, Olaf (Author) , Jansen, Andreas (Author) , Krug, Axel (Author) , Nenadić, Igor (Author) , Baune, Bernhard T. (Author) , Rietschel, Marcella (Author) , Witt, Stephanie (Author) , Forstner, Andreas Josef (Author) , Nöthen, Markus Maria (Author) , Johnen, Andreas (Author) , Alferink, Judith (Author) , Kircher, Tilo (Author) , Dannlowski, Udo (Author) , Opel, Nils (Author)
Format: Article (Journal)
Language:English
Published: May 2021
In: European neuropsychopharmacology
Year: 2021, Volume: 46, Pages: 93-104
ISSN:1873-7862
DOI:10.1016/j.euroneuro.2021.02.006
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.euroneuro.2021.02.006
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S0924977X21001358
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Author Notes:Janik Goltermann, Jonathan Repple, Ronny Redlich, Katharina Dohm, Claas Flint, Dominik Grotegerd, Lena Waltemate, Hannah Lemke, Stella Mercedes Fingas, Susanne Meinert, Verena Enneking, Tim Hahn, Jochen Bauer, Simon Schmitt, Tina Meller, Frederike Stein, Katharina Brosch, Olaf Steinsträter, Andreas Jansen, Axel Krug, Igor Nenadić, Bernhard T. Baune, Marcella Rietschel, Stephanie Witt, Andreas J. Forstner, Markus Nöthen, Andreas Johnen, Judith Alferink, Tilo Kircher, Udo Dannlowski, Nils Opel
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Summary:Apolipoprotein E (APOE) genotype is the strongest single gene predictor of Alzheimer's disease (AD) and has been frequently associated with AD-related brain structural alterations before the onset of dementia. While previous research has primarily focused on hippocampal morphometry in relation to APOE, sporadic recent findings have questioned the specificity of the hippocampus and instead suggested more global effects on the brain. With the present study we aimed to investigate associations between homozygous APOE ε4 status and cortical gray matter structure as well as white matter microstructure. In our study, we contrasted n = 31 homozygous APOE ε4 carriers (age=34.47 years, including a subsample of n = 12 subjects with depression) with a demographically matched sample without an ε4 allele (resulting total sample: N = 62). Morphometry analyses included a) Freesurfer based cortical segmentations of thickness and surface area measures and b) tract based spatial statistics of DTI measures. We found pronounced and widespread reductions in cortical surface area of ε4 homozygotes in 57 out of 68 cortical brain regions. In contrast, no differences in cortical thickness were observed. Furthermore, APOE ε4 homozygous carriers showed significantly lower fractional anisotropy in the corpus callosum, the right internal and external capsule, the left corona radiata and the right fornix. The present findings support a global rather than regionally specific effect of homozygous APOE ε4 allele status on cortical surface area and white matter microstructure. Future studies should aim to delineate the clinical implications of these findings.
Item Description:Gesehen am 14.10.2021
Physical Description:Online Resource
ISSN:1873-7862
DOI:10.1016/j.euroneuro.2021.02.006

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