caa a22 4500 606202188 CHVBK 20210128100952.0 cr unu---uuuuu 210128e20150501xx s 000 0 eng 10.1007/s00429-014-0738-4 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0738-4 Impacts of PICALM and CLU variants associated with Alzheimer's disease on the functional connectivity of the hippocampus in healthy young adults [Elektronische Daten] [Peng Zhang, Wen Qin, Dawei Wang, Bing Liu, Yunting Zhang, Tianzi Jiang, Chunshui Yu] PICALM rs3851179 and CLU rs11136000 have been recently associated with Alzheimer's disease (AD). Investigating the effects of these genetic variants on the resting-state functional connectivity (rsFC) of the hippocampus may provide new insight into AD pathogenesis. We investigated the main effects and interactions of these two genetic variants on hippocampal rsFC in 283 healthy young adults. The hippocampus showed positive rsFC with the default mode network and negative rsFC with the fronto-parietal network. Risk PICALM G-allele carriers showed weaker negative rsFC compared with AA carriers, whereas risk CLU-CC carriers exhibited stronger positive and negative rsFC than T-allele carriers. There existed complex interactions between PICALM and CLU on the negative rsFC of the hippocampus. Moreover, we found an allele-dependent effect of CLU on hippocampal connectivity when an additive genetic model was applied to CLU. Most of these effects remained significant even after controlling for individual ApoE status. Our results suggest that PICALM and CLU risk genotypes exert differential impacts on the hippocampal rsFC in healthy young subjects. The complex interactions between PICALM and CLU should be considered when investigating the impact of these two genetic variants on the brain. Springer-Verlag Berlin Heidelberg, 2014 PICALM nationallicence CLU nationallicence Hippocampus nationallicence Functional connectivity nationallicence FMRI nationallicence SNP nationallicence Zhang Peng Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China aut Qin Wen Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China aut Wang Dawei Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China aut Liu Bing Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China aut Zhang Yunting Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China aut Jiang Tianzi Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China aut Yu Chunshui Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China aut Brain Structure and Function Springer Berlin Heidelberg 220/3(2015-05-01), 1463-1475 1863-2653 220:3<1463 2015 220 429 https://doi.org/10.1007/s00429-014-0738-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0738-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhang Peng Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China aut NATIONALLICENCE 700 1- Qin Wen Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China aut NATIONALLICENCE 700 1- Wang Dawei Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China aut NATIONALLICENCE 700 1- Liu Bing Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China aut NATIONALLICENCE 700 1- Zhang Yunting Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China aut NATIONALLICENCE 700 1- Jiang Tianzi Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, China aut NATIONALLICENCE 700 1- Yu Chunshui Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, 300052, Tianjin, China aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/3(2015-05-01), 1463-1475 1863-2653 220:3<1463 2015 220 429