A Multi-Cohort Study of ApoE ɛ4 and Amyloid-β Effects on the Hippocampus in Alzheimer's Disease
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A Multi-Cohort Study of ApoE ɛ4 and Amyloid-β Effects on the Hippocampus in Alzheimer's Disease. / Khan, Wasim; Giampietro, Vincent; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Büchel, Christian; Conrod, Patricia; Flor, Herta; Frouin, Vincent; Garavan, Hugh; Gowland, Penny; Heinz, Anreas; Ittermann, Bernd; Lemaître, Hervé; Nees, Frauke; Paus, Tomas; Pausova, Zdenka; Rietschel, Marcella; Smolka, Michael N; Ströhle, Andreas; Gallinat, Jeurgen; Vellas, Bruno; Soininen, Hilkka; Kloszewska, Iwona; Tsolaki, Magda; Mecocci, Patrizia; Spenger, Christian; Villemagne, Victor L; Masters, Colin L; Muehlboeck, J-Sebastian; Bäckman, Lars; Fratiglioni, Laura; Kalpouzos, Grégoria; Wahlund, Lars-Olof; Schumann, Gunther; Lovestone, Simon; Williams, Steven C R; Westman, Eric; Simmons, Andrew; Alzheimer’s Disease Neuroimaging Initiative.
in: J ALZHEIMERS DIS, Jahrgang 56, Nr. 3, 2017, S. 1159-1174.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A Multi-Cohort Study of ApoE ɛ4 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
AU - Alzheimer’s Disease Neuroimaging Initiative
PY - 2017
Y1 - 2017
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 ɛ4 carriers with positron emission tomography Aβ who were dichotomized (Aβ+/Aβ-) using previous cut-offs. We found a linear reduction in hippocampal volumes with ɛ4 carriers possessing the smallest volumes, ɛ3 carriers possessing intermediate volumes, and ɛ2 carriers possessing the largest volumes. Moreover, AD and MCI ɛ4 carriers possessed the smallest hippocampal volumes and control ɛ2 carriers possessed the largest hippocampal volumes. Subjects with both APOE ɛ4 and Aβ+ had the lowest hippocampal volumes when compared to Aβ- ɛ4 carriers, suggesting a synergistic relationship between APOE ɛ4 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 ɛ4 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 ɛ4 carriers with positron emission tomography Aβ who were dichotomized (Aβ+/Aβ-) using previous cut-offs. We found a linear reduction in hippocampal volumes with ɛ4 carriers possessing the smallest volumes, ɛ3 carriers possessing intermediate volumes, and ɛ2 carriers possessing the largest volumes. Moreover, AD and MCI ɛ4 carriers possessed the smallest hippocampal volumes and control ɛ2 carriers possessed the largest hippocampal volumes. Subjects with both APOE ɛ4 and Aβ+ had the lowest hippocampal volumes when compared to Aβ- ɛ4 carriers, suggesting a synergistic relationship between APOE ɛ4 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 ɛ4 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 - Journal Article
U2 - 10.3233/JAD-161097
DO - 10.3233/JAD-161097
M3 - SCORING: Journal article
C2 - 28157104
VL - 56
SP - 1159
EP - 1174
JO - J ALZHEIMERS DIS
JF - J ALZHEIMERS DIS
SN - 1387-2877
IS - 3
ER -
