A Multi-Cohort Study of ApoE ϵ 4 and Amyloid-β Effects on the Hippocampus in Alzheimer's Disease

Wasim Khan; Vincent Giampietro; Tobias Banaschewski; Gareth J. Barker; Arun L W Bokde; Christian Büchel; Patricia Conrod; Herta Flor; Vincent Frouin; Hugh Garavan; Penny Gowland; Anreas Heinz; Bernd Ittermann; Hervé Lemaître; Frauke Nees; Tomas Paus; Zdenka Pausova; Marcella Rietschel; Michael N. Smolka; Andreas Ströhle; Jeurgen Gallinat; Bruno Vellas; Hilkka Soininen; Iwona Kloszewska; Magda Tsolaki; Patrizia Mecocci; Christian Spenger; Victor L. Villemagne; Colin L. Masters; J. Sebastian Muehlboeck; Lars Bäckman; Laura Fratiglioni; Grégoria Kalpouzos; Lars Olof Wahlund; Gunther Schumann; Simon Lovestone; Steven C R Williams; Eric Westman; Andrew Simmons

doi:10.3233/JAD-161097

A Multi-Cohort Study of ApoE ϵ 4 and Amyloid-β Effects on the Hippocampus in Alzheimer's Disease

Wasim Khan, Vincent Giampietro, Tobias Banaschewski, Gareth J. Barker, Arun L W Bokde, Christian Büchel, Patricia Conrod, Herta Flor, Vincent Frouin, Hugh Garavan, Penny Gowland, Anreas Heinz, Bernd Ittermann, Hervé Lemaître, Frauke Nees, Tomas Paus, Zdenka Pausova, Marcella Rietschel, Michael N. Smolka, Andreas StröhleJeurgen Gallinat, Bruno Vellas, Hilkka Soininen, Iwona Kloszewska, Magda Tsolaki, Patrizia Mecocci, Christian Spenger, Victor L. Villemagne, Colin L. Masters, J. Sebastian Muehlboeck, Lars Bäckman, Laura Fratiglioni, Grégoria Kalpouzos, Lars Olof Wahlund, Gunther Schumann, Simon Lovestone, Steven C R Williams, Eric Westman, Andrew Simmons^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

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Abstract

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-β (Aβ) 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 compared 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 ϵ4 carriers with positron emission tomography Aβ who were dichotomized (Aβ/Aβ-) using previous cut-offs. We found a linear reduction in hippocampal volumes with ϵ4 carriers possessing the smallest volumes, ϵ3 carriers possessing intermediate volumes, and ϵ2 carriers possessing the largest volumes. Moreover, AD and MCI ϵ4 carriers possessed the smallest hippocampal volumes and control ϵ2 carriers possessed the largest hippocampal volumes. Subjects with both APOE ϵ4 and Aβ had the lowest hippocampal volumes when compared to Aβ- ϵ4 carriers, suggesting a synergistic relationship between APOE ϵ4 and Aβ. 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 ϵ4 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.

Original language	English
Pages (from-to)	1159-1174
Number of pages	16
Journal	JOURNAL OF ALZHEIMERS DISEASE
Volume	56
Issue number	3
DOIs	https://doi.org/10.3233/JAD-161097
Publication status	Published - 3 Feb 2017

Keywords

Alzheimer's disease
amyloid
APOE 4
hippocampus
magnetic resonance imaging
mild cognitive impairment

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Khan, W., Giampietro, V., Banaschewski, T., Barker, G. J., Bokde, A. L. W., Büchel, C., Conrod, P., Flor, H., Frouin, V., Garavan, H., Gowland, P., Heinz, A., Ittermann, B., Lemaître, H., Nees, F., Paus, T., Pausova, Z., Rietschel, M., Smolka, M. N., ... Simmons, A. (2017). A Multi-Cohort Study of ApoE ϵ 4 and Amyloid-β Effects on the Hippocampus in Alzheimer's Disease. JOURNAL OF ALZHEIMERS DISEASE, 56(3), 1159-1174. https://doi.org/10.3233/JAD-161097

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abstract = "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-β (Aβ) 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 compared 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 ϵ4 carriers with positron emission tomography Aβ who were dichotomized (Aβ/Aβ-) using previous cut-offs. We found a linear reduction in hippocampal volumes with ϵ4 carriers possessing the smallest volumes, ϵ3 carriers possessing intermediate volumes, and ϵ2 carriers possessing the largest volumes. Moreover, AD and MCI ϵ4 carriers possessed the smallest hippocampal volumes and control ϵ2 carriers possessed the largest hippocampal volumes. Subjects with both APOE ϵ4 and Aβ had the lowest hippocampal volumes when compared to Aβ- ϵ4 carriers, suggesting a synergistic relationship between APOE ϵ4 and Aβ. 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 ϵ4 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.",

keywords = "Alzheimer's disease, amyloid, APOE 4, hippocampus, magnetic resonance imaging, mild cognitive impairment",

author = "Wasim Khan and Vincent Giampietro and Tobias Banaschewski and Barker, {Gareth J.} and Bokde, {Arun L W} and Christian B{\"u}chel and Patricia Conrod and Herta Flor and Vincent Frouin and Hugh Garavan and Penny Gowland and Anreas Heinz and Bernd Ittermann and Herv{\'e} Lema{\^i}tre and Frauke Nees and Tomas Paus and Zdenka Pausova and Marcella Rietschel and Smolka, {Michael N.} and Andreas Str{\"o}hle and Jeurgen Gallinat and Bruno Vellas and Hilkka Soininen and Iwona Kloszewska and Magda Tsolaki and Patrizia Mecocci and Christian Spenger and Villemagne, {Victor L.} and Masters, {Colin L.} and Muehlboeck, {J. Sebastian} and Lars B{\"a}ckman and Laura Fratiglioni and Gr{\'e}goria Kalpouzos and Wahlund, {Lars Olof} and Gunther Schumann and Simon Lovestone and Williams, {Steven C R} and Eric Westman and Andrew Simmons",

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doi = "10.3233/JAD-161097",

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Khan, W , Giampietro, V, Banaschewski, T, Barker, GJ, Bokde, ALW, Büchel, C, Conrod, P, Flor, H, Frouin, V, Garavan, H, Gowland, P, Heinz, A, Ittermann, B, Lemaître, H, Nees, F, Paus, T, Pausova, Z, Rietschel, M, Smolka, MN, Ströhle, A, Gallinat, J, Vellas, B, Soininen, H, Kloszewska, I, Tsolaki, M, Mecocci, P, Spenger, C, Villemagne, VL, Masters, CL, Muehlboeck, JS, Bäckman, L, Fratiglioni, L, Kalpouzos, G, Wahlund, LO, Schumann, G, Lovestone, S , Williams, SCR, Westman, E & Simmons, A 2017, 'A Multi-Cohort Study of ApoE ϵ 4 and Amyloid-β Effects on the Hippocampus in Alzheimer's Disease', JOURNAL OF ALZHEIMERS DISEASE, vol. 56, no. 3, pp. 1159-1174. https://doi.org/10.3233/JAD-161097

TY - JOUR

T1 - A Multi-Cohort Study of ApoE ϵ 4 and Amyloid-β Effects on the Hippocampus in Alzheimer's Disease

AU - Khan, Wasim

AU - Giampietro, Vincent

AU - Banaschewski, Tobias

AU - Barker, Gareth J.

AU - Bokde, Arun L W

AU - Büchel, Christian

AU - Conrod, Patricia

AU - Flor, Herta

AU - Frouin, Vincent

AU - Garavan, Hugh

AU - Gowland, Penny

AU - Heinz, Anreas

AU - Ittermann, Bernd

AU - Lemaître, Hervé

AU - Nees, Frauke

AU - Paus, Tomas

AU - Pausova, Zdenka

AU - Rietschel, Marcella

AU - Smolka, Michael N.

AU - Ströhle, Andreas

AU - Gallinat, Jeurgen

AU - Vellas, Bruno

AU - Soininen, Hilkka

AU - Kloszewska, Iwona

AU - Tsolaki, Magda

AU - Mecocci, Patrizia

AU - Spenger, Christian

AU - Villemagne, Victor L.

AU - Masters, Colin L.

AU - Muehlboeck, J. Sebastian

AU - Bäckman, Lars

AU - Fratiglioni, Laura

AU - Kalpouzos, Grégoria

AU - Wahlund, Lars Olof

AU - Schumann, Gunther

AU - Lovestone, Simon

AU - Williams, Steven C R

AU - Westman, Eric

AU - Simmons, Andrew

PY - 2017/2/3

Y1 - 2017/2/3

N2 - 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-β (Aβ) 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 compared 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 ϵ4 carriers with positron emission tomography Aβ who were dichotomized (Aβ/Aβ-) using previous cut-offs. We found a linear reduction in hippocampal volumes with ϵ4 carriers possessing the smallest volumes, ϵ3 carriers possessing intermediate volumes, and ϵ2 carriers possessing the largest volumes. Moreover, AD and MCI ϵ4 carriers possessed the smallest hippocampal volumes and control ϵ2 carriers possessed the largest hippocampal volumes. Subjects with both APOE ϵ4 and Aβ had the lowest hippocampal volumes when compared to Aβ- ϵ4 carriers, suggesting a synergistic relationship between APOE ϵ4 and Aβ. 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 ϵ4 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.

AB - 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-β (Aβ) 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 compared 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 ϵ4 carriers with positron emission tomography Aβ who were dichotomized (Aβ/Aβ-) using previous cut-offs. We found a linear reduction in hippocampal volumes with ϵ4 carriers possessing the smallest volumes, ϵ3 carriers possessing intermediate volumes, and ϵ2 carriers possessing the largest volumes. Moreover, AD and MCI ϵ4 carriers possessed the smallest hippocampal volumes and control ϵ2 carriers possessed the largest hippocampal volumes. Subjects with both APOE ϵ4 and Aβ had the lowest hippocampal volumes when compared to Aβ- ϵ4 carriers, suggesting a synergistic relationship between APOE ϵ4 and Aβ. 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 ϵ4 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.

KW - Alzheimer's disease

KW - amyloid

KW - APOE 4

KW - hippocampus

KW - magnetic resonance imaging

KW - mild cognitive impairment

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U2 - 10.3233/JAD-161097

DO - 10.3233/JAD-161097

M3 - Article

C2 - 28157104

SN - 1387-2877

VL - 56

SP - 1159

EP - 1174

JO - JOURNAL OF ALZHEIMERS DISEASE

JF - JOURNAL OF ALZHEIMERS DISEASE

IS - 3

ER -

A Multi-Cohort Study of ApoE ϵ 4 and Amyloid-β Effects on the Hippocampus in Alzheimer's Disease

Abstract

Keywords

UN SDGs

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