Tract Based Spatial Statistic Reveals No Differences in White Matter Microstructural Organization between Carriers and Non-Carriers of the APOE ɛ4 and ɛ2 Alleles in Young Healthy Adolescents

TY - JOUR

T1 - Tract Based Spatial Statistic Reveals No Differences in White Matter Microstructural Organization between Carriers and Non-Carriers of the APOE ɛ4 and ɛ2 Alleles in Young Healthy Adolescents

AU - Dell'Acqua, Flavio

AU - Khan, Wasim

AU - Gottlieb, Natalie

AU - Giampietro, Vincent

AU - Ginestet, Cedric

AU - Bouls, David

AU - Newhouse, Steven

AU - Dobson, Richard

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 - Lemaítre, Hervé

AU - Nees, Frauke

AU - Paus, Tomas

AU - Pausova, Zdenka

AU - Rietschel, Marcella

AU - Smolka, Michael N

AU - Ströhle, Andreas

AU - Gallinat, Jean

AU - Westman, Eric

AU - Schumann, Gunther

AU - Lovestone, Simon

AU - Simmons, Andrew

PY - 2015/8/11

Y1 - 2015/8/11

N2 - The apolipoprotein E (APOE) ɛ4 allele is the best established genetic risk factor for Alzheimer's disease (AD) and has been previously associated with alterations in structural gray matter and changes in functional brain activity in healthy middle-aged individuals and older non-demented subjects. In order to determine the neural mechanism by which APOE polymorphisms affect white matter (WM) structure, we investigated the diffusion characteristics of WM tracts in carriers and non-carriers of the APOE ɛ4 and ɛ2 alleles using an unbiased whole brain analysis technique (Tract Based Spatial Statistics) in a healthy young adolescent (14 years) cohort. A large sample of healthy young adolescents (n = 575) were selected from the European neuroimaging-genetics IMAGEN study with available APOE status and accompanying diffusion imaging data. MR Diffusion data was acquired on 3T systems using 32 diffusion-weighted (DW) directions and 4 non-DW volumes (b-value = 1,300 s/mm2 and isotropic resolution of 2.4×2.4×2.4 mm). No significant differences in WM structure were found in diffusion indices between carriers and non-carriers of the APOE ɛ4 and ɛ2 alleles, and dose-dependent effects of these variants were not established, suggesting that differences in WM structure are not modulated by the APOE polymorphism. In conclusion, our results suggest that microstructural properties of WM structure are not associated with the APOE ɛ4 and ɛ2 alleles in young adolescence, suggesting that the neural effects of these variants are not evident in 14-year-olds and may only develop later in life.

AB - The apolipoprotein E (APOE) ɛ4 allele is the best established genetic risk factor for Alzheimer's disease (AD) and has been previously associated with alterations in structural gray matter and changes in functional brain activity in healthy middle-aged individuals and older non-demented subjects. In order to determine the neural mechanism by which APOE polymorphisms affect white matter (WM) structure, we investigated the diffusion characteristics of WM tracts in carriers and non-carriers of the APOE ɛ4 and ɛ2 alleles using an unbiased whole brain analysis technique (Tract Based Spatial Statistics) in a healthy young adolescent (14 years) cohort. A large sample of healthy young adolescents (n = 575) were selected from the European neuroimaging-genetics IMAGEN study with available APOE status and accompanying diffusion imaging data. MR Diffusion data was acquired on 3T systems using 32 diffusion-weighted (DW) directions and 4 non-DW volumes (b-value = 1,300 s/mm2 and isotropic resolution of 2.4×2.4×2.4 mm). No significant differences in WM structure were found in diffusion indices between carriers and non-carriers of the APOE ɛ4 and ɛ2 alleles, and dose-dependent effects of these variants were not established, suggesting that differences in WM structure are not modulated by the APOE polymorphism. In conclusion, our results suggest that microstructural properties of WM structure are not associated with the APOE ɛ4 and ɛ2 alleles in young adolescence, suggesting that the neural effects of these variants are not evident in 14-year-olds and may only develop later in life.

U2 - 10.3233/JAD-140519

DO - 10.3233/JAD-140519

M3 - SCORING: Journal article

C2 - 26401776

VL - 47

SP - 977

EP - 984

JO - J ALZHEIMERS DIS

JF - J ALZHEIMERS DIS

SN - 1387-2877

IS - 4

ER -